System, method, and apparatus for utilizing a pumping cassette

ABSTRACT

The present invention involves, in some embodiments, systems and methods for pumping fluid into or out of a patient via a cartridge. The cartridge may include a membrane defining a chamber and mechanisms to supply, measure and control pressure in the chamber. The system further includes a processor that can be configured to compare certain pressure measurements to each other to facilitate determining if an error condition exists in the medical system if the difference between measurements is greater than a threshold. In certain cases the error condition may indicate leakage of the membrane, for example due to a pinhole in the membrane.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/973,630, filed Aug. 22, 2013, which is a continuation of U.S.application Ser. No. 12/847,980, filed Jul. 30, 2010, now allowed, whichis a division of U.S. application Ser. No. 12/423,665, filed Apr. 14,2009 and issued on Aug. 3, 2010 as U.S. Pat. No. 7,766,301, which is acontinuation of U.S. application Ser. No. 10/951,441, filed Sep. 28,2004 and issued on Jul. 14, 2009 as U.S. Pat. No. 7,559,524, which is acontinuation of U.S. application Ser. No. 09/357,645, filed Jul. 20,1999, and issued on Apr. 12, 2005 as U.S. Pat. No. 6,877,713, each ofwhich is herein incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates generally to systems and methods formetering, pumping, or handling fluids. The invention, in someembodiments is especially well suited to systems and methods for medicalinfusion and fluid handling.

BACKGROUND OF THE INVENTION

A wide variety of applications in industrial and medical fields requirefluid metering and pumping systems able to deliver precisely measuredquantities of fluids at accurate flow rates to various destinations. Inthe medical field especially, precise and accurate fluid delivery iscritical for many medical treatment protocols. Medical infusion andfluid-handling systems for use in the pumping or metering fluids toand/or from the body of a patient typically require a high degree ofprecision and accuracy in measuring and controlling fluid flow rates andvolumes. For example, when pumping medicaments or other agents to thebody of a patient, an infusion flow rate which is too low may proveineffectual, while an infusion flow rate which is too high may provedetrimental or toxic to the patient.

Pumping and fluid metering systems for use in medical applications, forexample in pumping fluids to and/or from the body of a patient, areknown in the art. Many of such prior art systems comprise peristaltic orsimilar type pumping systems. Such prior art systems typically deliverfluid by compressing and/or collapsing a flexible tube or other flexiblecomponent containing the fluid to be pumped. While such known systemsare sometimes adequate for certain applications, precise and accurateflow rates in such systems can be difficult to measure and control dueto factors such as distortion of the walls of collapsible tubing orcomponents of the systems, changes in relative heights of the patientand fluid supply, changes in fluid supply line or delivery lineresistance, and other factors.

Another shortcoming of such prior art systems is that it is oftendifficult to determine and maintain accurate volumetric flow rates inreal time during operation of the infusion system. Typically, many suchprior art systems utilize volume and flow rate measurement techniquesthat, in some cases, can have lower accuracy than desirable, or arecumbersome and difficult to implement and cannot be performed in realtime as the system is operating. Some approaches which have been used insuch prior art systems for measuring volumes and flow rates includeoptical drop counting, the weighing of chambers containing infusionliquids, and other approaches.

Many such prior art infusion systems also employ valving systems whichcomprise clamps, or other pinching devices, which open and close a lineby pinching or collapsing the walls of tubing. Such valving arrangementscan have several shortcomings for applications involving medicalinfusion including difficulties in obtaining a fluid-tight seal anddistortion of the walls of the tubing, which can lead to undesirablefluid leakage and/or irregular flow rates.

In addition, many typical prior art infusion systems, such as thosedescribed above, are constrained to fairly simple fluid handling tasks,such as providing a single or, in some cases, several individual flowpaths between one or more fluid sources and a patient. Such prior artsystems are not well suited for performing complex, multi-functionalfluid handling and pumping tasks and often do not have sufficientoperating flexibility to be used for a wide variety of fluid handlingapplications, without significant rearranging or retooling of thecomponents of the system.

Also, for medical infusion applications involving the pumping ormetering of fluids to the body of a patient, it is important to detectair present in a line pumping fluid to the body of a patient and toprevent such air from entering the body of the patient. Typically, priorart infusion systems employed for such applications detect the presenceof air in the system by relying only on external air detectioncomponents, for example ultrasonic detectors, which are typicallydownstream of a pump and immediately upstream of the patient. Also, forsuch systems, once air has been detected in the line, purging the airfrom the line before it reaches the patient may require manualintervention and, in some cases, disconnection of lines within thesystem.

For pumping and infusion systems utilized for pumping fluids to the bodyof a patient, it is also typically desirable to pass fluids through afilter or screen prior to their entering the body of the patient inorder to remove any insoluble clumps, or aggregates of materialtherefrom that may be detrimental to the patient if infused into thebody. Such filters are especially important when pumping blood or bloodcomponents to the body of a patient; in which case, the filters serveprimarily as blood clot filters to remove clots or aggregated cells fromthe blood or blood components. Prior art infusion systems used for suchapplications can include blood clot/particulate filters outside thepumping component of the system, installed on the line providing infusedfluid to the patient. Such assembly requires additional setup time andattention from an operator of the system and often results in anotherpotential location of fluid leakage or site of contamination within thesystem.

While the above mentioned and other prior art pumping and fluid handlingsystems represent, in some instances, useful tools in the art of fluidhandling and pumping there remains a need in the art to: (a) providepumping and fluid metering systems which have an improved ability tocontrol and measure volumes and flow rates; (b) provide improved valvingsystems; (c) provide increased flexibility for multiple uses; and (d)include air detection capability and integrated fluid filtration.Certain embodiments of the present invention address one or more of theabove needs.

SUMMARY OF THE INVENTION

Certain embodiments of the present invention provide a series of pumpingsystems, methods for operating the systems, and components of thesystems. These embodiments include, in one aspect, a series of systemsfor measuring the volume of a volumetric chamber, detecting the presenceof a gas in a pump chamber, and/or pumping a liquid with a pump chamber.Some embodiments of the present invention include a series of methodsfor pumping a liquid at a desired average flow rate with a pumpingcartridge of a pumping system. Some embodiments of the present inventionprovide a series of pumping cartridges and pump chambers, and methodsfor operating such cartridges and chambers.

According to one embodiment of the present invention, a method andcorresponding system for detecting the presence of a gas in a pumpchamber is disclosed. The pump chamber may be an isolatable pumpchamber. According to this embodiment, the method includes the steps of:isolating the pump chamber; determining a first measured parameterrelated to the volume of the pump chamber with at least a first forcesupplied to a surface of the pump chamber; determining a second measuredparameter related to the volume of the pump chamber with at least asecond force applied to the surface of the pump chamber; and thencomparing the first measured parameter and the second measuredparameter.

In another embodiment, a method for detecting the presence of a gas in apump chamber is disclosed, where the pump chamber is coupled to orcontained within a control chamber. In this embodiment, the methodcomprises: supplying a measurement gas to the control chamber at a firstmeasured pressure; changing the pressure of the measurement gas in thecontrol chamber to a second measured pressure; supplying a measurementgas to the control chamber at a third measured pressure; changing thepressure of the measurement gas in the control chamber to a fourthmeasured pressure; and determining the presence of a gas in the pumpchamber based at least in part on the measured pressures.

In yet another embodiment, a method for detecting the presence of gas ina pump chamber is disclosed, where the pump chamber is coupled to orcontained within a control chamber. The method comprises determining afirst measured parameter related to the volume of the pump chamberand/or the control chamber with a fluid supplied to the control chamberat a first pressure, determining a second measured parameter related tothe volume of the pump chamber and/or the control chamber with a fluidsupplied to the control chamber at a second pressure, and comparing thefirst measured parameter and the second measured parameter.

In yet another embodiment, a method for detecting the presence of gas ina pump chamber is disclosed, where the pump chamber is at leastpartially comprised of a movable surface. The method comprisesdetermining a first measured parameter related to a volume of the pumpchamber with at least a first force applied to the movable surface,where the first force creates a first level of stress in the movablesurface. The method further comprises determining a second measuredparameter related to a volume of the pump chamber with at least a secondforce applied to the movable surface, where the second force creates asecond level of stress in the movable surface. The method furthercomprises comparing the first measured parameter and the second measuredparameter.

In another embodiment, a method for detecting the presence of a gas in apump chamber is disclosed, where the pump chamber is at least partiallycomprised of a movable surface and is coupled to or contained within acontrol chamber. The method comprises: supplying a measurement gas tothe control chamber at a first measured pressure, where the firstmeasured pressure creates a first difference in pressure between thepump chamber and the control chamber; supplying a measurement gas to thecontrol chamber at a second measured pressure, where the second measuredpressure creates a second difference in pressure between the pumpchamber and the control chamber; and determining the presence of a gasin the pump chamber based at least in part on the measured pressures.

In another embodiment, a system for detecting the presence of a gas inan isolatable pump chamber is disclosed. In this embodiment, the systemincludes a force applicator that is constructed and arranged to apply aforce to a surface of the pump chamber at least a first level of forceand a second level of force. The system further includes a comparerconfigured to determined the presence of a gas in the pump chamber basedat least in part on a first measured parameter related to the volume ofthe pump chamber at a first condition, and a second measured parameterrelated to the volume of the pump chamber at a second condition.

In another embodiment, a system for detecting the presence of a gas in apump chamber is disclosed. The system in this embodiment includes acontrol chamber that is coupled to or contains the pump chamber, aflexible membrane comprising at least a portion of the pump chamber, andat least one pressure measuring component able to measure a pressure inthe control chamber. The system further includes a fluid supply systemin fluid communication with the control chamber that is able to supply afluid to the control chamber at at least a first and a secondpredetermined pressure, where the fluid pressure in the control chamberis measured with the pressure measuring component. The system in thisembodiment also includes a comparer configured to determine the presenceof a gas in the pump chamber based on a first measured parameter relatedto a volume of the control chamber at at least the first pressure and asecond measured parameter related to the volume of a control chamber atat least the second pressure.

In yet another embodiment, a system for detecting the presence of a gasin a pump chamber is disclosed. The system in this embodiment includes acontrol chamber that is coupled to or contains the pump chamber, apressure supply to pressurize the control chamber at at least a firstpressure and a second pressure, and a comparer that is configured todetermine the presence of gas in the pump chamber based at least in parton a first measured parameter related to a volume of the pump chamberand/or control chamber at a first condition, and a second measuredparameter related to a volume of a pump chamber and/or control chamberat a second condition.

In another embodiment, a system for detecting the presence of a gas in apump chamber is disclosed. The system in this embodiment comprises forceapplicator means for supplying a force to the surface of the pumpchamber at a first level of force and a second level of force, andprocessor means for determining the presence of a gas in the pumpchamber based at least in part on a first measured parameter related tothe volume of the pump chamber at a first condition and a secondmeasured parameter related to the volume of the pump chamber at a secondcondition.

In another embodiment, a pump chamber is disclosed. The pump chamber inthis embodiment includes a wall and a movable surface comprising atleast a portion of the wall. The pump chamber further includes at leastone spacer positioned within the pump chamber to inhibit gas from beingpumped through the pump chamber.

In yet another embodiment, a pump chamber including a wall and aflexible membrane disposed over at least a portion of the wall isdisclosed. The pump chamber in this embodiment further includes at leastone spacer positioned within the pump chamber to assist air to rise inthe pump chamber.

In yet another embodiment, a pump chamber comprising a volumetriccontainer is disclosed. The pump chamber in this embodiment includes aflexible membrane comprising at least a portion of a wall of thecontainer, with at least one spacer positioned within the container toinhibit contact between internal surfaces of the container.

In another embodiment, a pump chamber is disclosed. The pump chamber isthis embodiment comprises a first movable wall of the pump chamber, asecond wall of the pump chamber, and at least one elongate spacerattached to the second wall and projecting towards the first movablewall.

In another embodiment, a method of pumping of fluid is disclosed. Themethod involves providing a pump chamber, which includes a flexiblemembrane, and preventing any gas contained within the pump chamber frombeing pumped from the pump chamber by providing at least one spacerelement within the pump chamber. The spacer element in this embodimentprevents the flexible membrane from contacting an internal surface ofthe pump chamber during pumping.

In another aspect, a series of pumping systems is disclosed. In oneembodiment, the system is for pumping a liquid with a pump chamber. Thesystem in this embodiment includes at least one fluid source, containinga fluid at a first pressure, where the source is able to be placed influid communication with a control chamber that is coupled to the pumpchamber when the system is in operation. The system in this embodimentfurther includes a variable sized orifice valve able to be placed influid communication with the fluid source and the control chamber. Thesystem may also include a processor which controls the variable sizedorifice valve to selectively allow the control chamber to be pressurizedwith a fluid from the fluid source to a desired pressure. In thisembodiment, the processor also controls the pressure within the controlchamber during filling of the pump chamber with a liquid or duringdischarge of a liquid from the pump chamber by selectively changing thesize of an orifice within the variable sized orifice valve.

In another embodiment, a method for pumping a liquid using a pumpchamber is disclosed. The method comprises: providing a first fluidsource that supplies a fluid at a first pressure in fluid communicationwith an inlet of a variable sized orifice valve; providing a controlchamber that is coupled to the pump chamber, where the control chamberis in fluid communication with an outlet of the variable sized orificevalve; selectively changing a size of an orifice within the variablesized orifice valve in order to pressurize the control chamber with thefluid to a desired pressure; and maintaining the desired pressure in thecontrol chamber by selectively changing the size of the orifice.

In another embodiment, a system for measuring the volume of a volumetricchamber is disclosed. The system includes a reference chamber, a firstfluid source supplying fluid at a first pressure, and a second fluidsource supplying fluid at a second pressure. The system in thisembodiment also includes a switch valve having a first and second inletand an outlet. The first inlet of the switch valve is connected in fluidcommunication with the first fluid source, and the second inlet of theswitch valve is connected in fluid communication with the second fluidsource. The outlet of the switch valve is connected in fluidcommunication with at least one line able to be placed in fluidcommunication with the reference chamber and the volumetric chamber. Theswitch valve has a first position that provides fluid communicationbetween the first fluid source and the reference chamber and volumetricchamber, and has a second position that provides fluid communicationbetween the second fluid source and the reference chamber and volumetricchamber. The system may also include a processor which controls theswitch valve to selectively allow the reference chamber and/or thevolumetric chamber to be pressurized to a selected pressure with a fluidfrom either the first fluid source or the second fluid source. Theprocessor also determines a volume of the volumetric chamber based atleast in part on the selected pressure.

In another embodiment, a method for measuring a volume of a volumetricchamber is disclosed. The method comprises providing a first fluidsource to supply fluid at a first pressure, a second fluid source tosupply fluid at a second pressure, and a switch-valve having a firstinlet, a second inlet, and an outlet, where the first inlet is connectedin fluid communication with the first fluid source, the second inlet isconnected in fluid communication with the second fluid source, and theoutlet is connected in fluid communication with at least one line thatis able to be placed in fluid communication with the volumetric chamber.The method further comprises positioning the switch valve to allow thevolumetric chamber to be pressurized with the fluid from the first fluidsource, determining a first pressure of the volumetric chamber, anddetermining a volume of the volumetric chamber based at least in part onthe first pressure.

In yet another embodiment, a system for pumping a liquid with a pumpchamber is disclosed. The system in this embodiment includes a firstfluid source supplying fluid at a first pressure, and a second fluidsource supplying fluid at a second pressure. The system in thisembodiment also includes a switch valve having a first and a secondinlet and an outlet. The first inlet is connected in fluid communicationwith the first fluid source, and the second inlet is connected in fluidcommunication with the second fluid source. The outlet of the switchvalve is connected in fluid communication with at least one line able tobe placed in fluid communication with a control chamber that is coupledto the pump chamber when the system is in operation. The switch valvehas a first position that provides fluid communication between the firstfluid source and the control chamber, and has a second position thatprovides fluid communication between the second fluid source and thecontrol chamber.

In another embodiment, a method for pumping a liquid with a pump chamberis disclosed. The method comprises providing a first fluid source tosupply fluid at a first pressure, a second fluid source to supply fluidat a second pressure, and a switch-valve having a first inlet, a secondinlet, and an outlet, where the first inlet is connected in fluidcommunication with the first fluid source, the second inlet is connectedin fluid communication with the second fluid source, and the outlet isconnected in fluid communication with at least one line able to beplaced in fluid communication with a control chamber to be coupled to apump chamber when the system is in operation. The method furthercomprises positioning the switch-valve to provide fluid communicationbetween the first fluid source and the control chamber so as to at leastpartially fill the pump chamber with a liquid, and positioning theswitch-valve to provide fluid communication between the second fluidsource and the control chamber for dispensing the liquid from the pumpchamber.

In yet another aspect, a series of methods and systems for pumping aliquid at a desired average flow rate with a pumping cartridge isdisclosed. In one embodiment, the method involves pumping a liquid at adesired average flow rate with a pumping cartridge, where the cartridgeincludes at least one pump chamber, at least a portion of which pumpchamber includes a movable surface. The method of this embodimentinvolves: at least partially filling the pump chamber with a liquid;isolating the pump chamber; applying a force to the movable surface andregulating the flow of liquid from the pump chamber while maintainingthe force on the surface.

In another embodiment, a method for pumping a liquid at a desiredaverage flow rate with a pumping cartridge that includes at least onepump chamber, at least a portion of which pump chamber comprises amovable surface is disclosed. The method of this embodiment involves:closing a valve positioned on an outlet line of the pump chamber; atleast partially filling the pump chamber with a liquid; closing a valvepositioned on the inlet line of the pump chamber thereby isolating thepump chamber; and, while maintaining the inlet valve in a closedposition, applying a force to the movable surface and opening the outletvalve for predetermined periods at predetermined intervals whilemaintaining the force on the movable surface. The predetermined timeperiods and intervals may be selected to yield a desired average flowrate.

In yet another embodiment, a fluid metering system is disclosed. Thesystem of this embodiment comprises a reusable component that isconstructed and arranged for operative association with a removablepumping cartridge by coupling to the pumping cartridge. The pumpingcartridge of this embodiment includes at least one pump chamber and hasan outlet line having an outlet valve therein. The fluid metering systemin this embodiment includes a processor that is configured to controlpulsing of the outlet valve to achieve a desired flow rate.

In yet another embodiment, a fluid metering system including a reusablecomponent that is constructed and arranged for operative associationwith a removable pumping cartridge is disclosed. The pumping cartridgeincludes at least one pump chamber having an inlet line having a firstvalve therein and an outlet line having a second valve therein. The pumpchamber is at least partially formed from a movable surface. The systemfurther includes valve actuating means for operating the first valve andthe second valve, and pump chamber actuating means for applying a forceto the movable surface. The system further includes control means forcontrolling the valve actuating means and pump chamber actuating meansto deliver fluid at a desired flow rate from the pump chamber by closingthe first valve, applying a force to the movable surface, and pulsingthe second valve.

In another embodiment, a series of pumping cartridges is disclosed. Inone embodiment, the pumping cartridge includes a first liquid flow path,a second liquid flow path, and a bypass valve in fluid communicationwith the first liquid flow path and the second liquid flow path. Thebypass valve is constructed and arranged to selectively permit liquidflow through the first liquid flow path or the second liquid flow path,or to prevent liquid flow through both the first liquid flow path andthe second liquid flow path.

In another embodiment, a pumping cartridge including a first componentand at least one membrane disposed on the first component is disclosed.The first component and the membrane define a bypass valving chamber.The bypass valving chamber in this embodiment includes three ports, twoof which ports are occludable by the membrane. The pumping cartridge inthis embodiment further includes a first fluid flow path entering thebypass valving chamber through a first port and exiting the bypassvalving chamber through a third occludable port. The pumping cartridgein this embodiment further includes a second fluid flow path enteringthe bypass valving chamber through a second occludable port and exitingthe bypass valving chamber through the first port.

In yet another embodiment, a reusable system is disclosed that isconstructed and arranged for operative association with a removablepumping cartridge, where the pumping cartridge provides at least twofluid flow paths therein and includes a bypass valving chamber in fluidcommunication with a first fluid flow path and a second fluid flow path.The system in this embodiment includes a pump housing component that isconstructed and arranged to couple to the pumping cartridge, and a valveactuator to actuate the bypass valving chamber. The valve actuator inthis embodiment is disposed within the pump housing adjacent to and inoperative association with the bypass valving chamber, when the pumpingcartridge is coupled to the pump housing

In yet another embodiment, a reusable system is disclosed that isconstructed and arranged for operative association with a removablepumping cartridge, where the pumping cartridge provides at least twoliquid flow paths therein and includes a first component, with at leastone membrane disposed on the first component. The first component andthe membrane define a bypass valving chamber. The reusable system inthis embodiment includes a pump housing component that is constructedand arranged for operative association with the pumping cartridge bycoupling to the pumping cartridge. The reusable system in thisembodiment also includes a valve actuator to actuate the bypass valvingchamber, which actuator is disposed adjacent to and in operativeassociation with the bypass valving chamber when the pumping cartridgeis coupled to the pump housing. The system may further include a forceapplicator forming at least a part of the valve actuator, where theforce applicator is constructed and arranged to alternatively: apply aforce to at least a portion of the membrane to restrict liquid flowthrough a first liquid flow path through the bypass valving chamber;apply a force to at least a portion of the membrane to restrict liquidflow through a second liquid flow path through the bypass valvingchamber; and apply a force to at least a portion of the membrane torestrict liquid flow through both the first and the second liquid flowpaths.

In another embodiment, a method for directing flow in a pumpingcartridge is disclosed, where the pumping cartridge includes a bypassvalving chamber having three ports therein and two liquid flow pathstherethrough. At least a portion of the bypass valving chamber in thisembodiment is formed from a membrane. The method in this embodimentcomprises occluding a first port disposed in the bypass valving chamberwith the membrane to restrict the flow of liquid through the bypassvalving chamber along a first flow path, or occluding a second portdisposed in the bypass valving chamber with the membrane to restrict theflow of liquid through the bypass valving chamber along a second flowpath, and/or occluding both the first and second ports disposed in thebypass valving chamber with the membrane to restrict the flow of liquidalong both the first and second flow paths.

In yet another aspect, pumping cartridges including filter elements andmethods for filtering fluids are disclosed. In one embodiment, aremovable pumping cartridge that is constructed and arranged foroperative association with the reusable component is provided, thecartridge including at least one pump chamber, at least one valvingchamber, and at least one fluid flow path constructed and positionedwithin the cartridge to provide fluid communication between the pumpchamber and a body of a patient when pumping a fluid thereto. Thecartridge in this embodiment further includes at least one filterelement in fluid communication with the fluid flow path.

In another embodiment, a method for filtering a liquid supplied to thevasculature of a patient is disclosed. The method in this embodimentincludes supplying a liquid to a pump chamber disposed in a removablepumping cartridge, where the pumping cartridge is constructed andarranged for operative association with a reusable component. The methodfurther involves pumping the liquid to the patient through a filterelement disposed in the pumping cartridge.

In yet another aspect, occluders for occluding collapsible tubing, andmethods for occluding collapsible tubing using such occluders aredisclosed. In one embodiment, an occluder for occluding at least onecollapsible tube is disclosed. The occluder in this embodiment comprisesan occluding member and a force actuator that is constructed andpositioned to bend the occluding member.

In another embodiment, a method for occluding at least one collapsibletube is disclosed. The method comprises applying a force to bend theoccluding member in order to open the collapsible tube to enable fluidto flow therethrough, and releasing the force in order to relax theoccluding member and occlude the collapsible tube.

Each of the above disclosed inventions and embodiments may be useful andapplied separately and independently, or may be applied in combination.Description of one aspect of the inventions are not intended to belimiting with respect to other aspects of the inventions.

Other advantages, novel features, and objects of the invention willbecome apparent from the following detailed description of the inventionwhen considered in conjunction with the accompanying drawings, which areschematic and are not intended to be drawn to scale. In the figures,identical or substantially similar components that are illustrated invarious figures may be represented by a single numeral. For purposes ofclarity, not every component is labeled in every figure, nor is everycomponent of each embodiment of the invention shown where illustrationis not necessary to allow those of ordinary skill in the art tounderstand the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a pumping system according to oneembodiment of the invention;

FIG. 2 is a schematic illustration of a fluid pump according to oneembodiment of the invention;

FIG. 3 a is a flow chart illustrating a series of steps in a pumpingcycle according to one embodiment of the invention;

FIG. 3 b is a flow chart illustrating a series of substeps of thepumping cycle of FIG. 3 a for performing volume calculation and airdetection;

FIG. 3 c is a flow chart illustrating a series of substeps of thepumping cycle of FIG. 3 a for detecting the presence of a gas in a pumpchamber;

FIG. 4 is a schematic illustration of the pump of FIG. 1 at a firstcondition of fluid pressure in the control chamber;

FIG. 5 is a schematic illustration of a pumping system according to oneembodiment of the invention;

FIG. 6 a is a flow chart illustrating a series of steps in a pumpingcycle according to one embodiment of the invention;

FIG. 6 b is a flow chart illustrating a series of substeps of thepumping cycle of FIG. 6 a for performing volume calculation and airdetection;

FIG. 6 c is a flow chart illustrating a series of substeps of thepumping cycle of FIG. 6 a for detecting the presence of a gas in a pumpchamber;

FIG. 7 is a schematic illustration of a pumping system according to oneembodiment of the invention;

FIG. 8 is a schematic illustration of a pumping system according to oneembodiment of the invention;

FIG. 9 a is a flow chart illustrating a series of steps in a pumpingcycle according to one embodiment of the invention;

FIG. 9 b is a flow chart illustrating a series of substeps of thepumping cycle of FIG. 9 a for performing volume calculation and airdetection;

FIG. 9 c is a flow chart illustrating a series of substeps of thepumping cycle of FIG. 9 a for detecting the presence of a gas in a pumpchamber;

FIG. 10 is a partially-cutaway cross-sectional illustration of aremovable pumping cartridge and pump housing component according to oneembodiment of the invention;

FIG. 11 a is a schematic illustration of a pumping cartridge accordingto one embodiment of the invention;

FIG. 11 b is a cross-sectional illustration of the pumping cartridge ofFIG. 11 a;

FIG. 11 c is a partially-cutaway cross-sectional illustration of a valveprovided by the pumping cartridge of FIG. 11 a;

FIG. 11 d is a partially-cutaway cross-sectional illustration of thevalve of FIG. 11 c, according to an alternative embodiment of theinvention;

FIG. 11 e is a partially-cutaway cross-sectional illustration of abypass valving chamber of the pumping cartridge of FIG. 11 a;

FIG. 11 f is a partially-cutaway cross-sectional illustration of thebypass valving chamber of FIG. 11 e, according to an alternativeembodiment of the invention;

FIG. 12 a is a schematic illustration of an occluder mechanism in anopen position, according to one embodiment of the invention;

FIG. 12 b is a schematic illustration of the occluder mechanism of FIG.12 a in a closed position;

FIG. 12 c is a schematic illustration of an occluder mechanism in anopen position, according to one embodiment of the invention;

FIG. 12 d is a schematic illustration of the occluder mechanism of FIG.12 c in a closed position;

FIG. 12 e is a schematic illustration of an occluder mechanism utilizinga spring plate, in an open position, according to one embodiment of theinvention;

FIG. 12 f is a schematic illustration of the occluder mechanism of FIG.12 e in a closed position; and

FIG. 13 is a schematic illustration of a flow diagram illustrating theoverall system architecture and control configuration for a pumpingsystem, according to one embodiment of the invention.

DETAILED DESCRIPTION

Certain embodiments of the present invention relate to a series ofmethods and systems useful in fluid pumping applications. Someembodiments of these methods and systems are especially useful forapplications involving the pumping of liquids to and from the body of apatient during a medical treatment or procedure. The need for pumpingliquids to and from the body of a patient arises in a wide variety ofmedical treatments and procedures including, for example, hemodialysisfor the treatment of kidney failure, plasmapheresis for separating bloodcells from plasma, general infusion of intervenous fluids and/ormedicaments, and a wide variety of additional treatments and proceduresapparent to those of ordinary skill in the art. The methods and systemsof the current invention may be advantageously utilized for any of theabove-mentioned liquid pumping applications, or any other fluid pumpingapplication, including various industrial applications, as apparent tothose of ordinary skill in the art.

Certain embodiments of the present invention relate to pumping systemsand methods for operating the pumping systems for pumping liquids with apump chamber. The term “pump” or “pumping” as used herein refers to theforcing, controlling or metering of the flow of a fluid through a lineeither by metering a flow of a fluid that is moving under the influenceof a pre-existing pressure drop within the line, or by forcing a fluidthrough a line by increasing the pressure of the fluid within the line.Many embodiments, as described in more detail below, involve systemswhere the pressure of the fluid being pumped is increased (e.g.,increased cyclically) by using a pump chamber and a source of mechanicalforce acting on one or more external surfaces of the pump chamber.

A “chamber” as used herein, for example in the context of a pumpchamber, refers to a volumetric container having a constant or variableinternal volume, which is able to contain a fluid. A “fluid” as usedherein can refer to a material that is either a liquid or gas.

The methods and systems provided in some embodiments of the presentinvention, in preferred embodiments, include pumping systems with pumpchambers having at least one moveable surface. A “moveable surface” asused herein in this context refers to a surface of a chamber that can bedisplaced by a force applied thereto, so as to change an internal volumeof the chamber. A non-limiting list of pumping systems that employ pumpchambers including at least one moveable surface include: diaphragmpumps, piston pumps, peristaltic pumps, flexible bulb pumps, collapsiblebag pumps, and a wide variety of other pump configurations, as apparentto those of ordinary skill in the art.

Preferred embodiments of the invention involve pumping systems includinga pump chamber which comprises an isolatable chamber. An “isolatablechamber” as used herein refers to a volumetric chamber or container forholding a fluid, which can isolate the fluid from fluid communicationwith fluids outside of the isolatable chamber (e.g., by sealing orclosing inlets and outlets to the chamber). The term “fluidcommunication” as used herein refers to two chambers, or othercomponents or regions containing a fluid, where the chambers,components, or regions are connected together (e.g., by a line, pipe, ortubing) so that a fluid can flow between the two chambers, components,or regions. Therefore, two chambers which are in “fluid communication”can, for example, be connected together by a line between the twochambers, such that a fluid can flow freely between the two chambers.For embodiments involving an isolatable chamber, for example anisolatable pump chamber, lines connecting the isolatable chamber toother chambers or regions of the pumping system may include at least onevalve (or other device) therein which may be closed, or occluded, inorder to block fluid communication between the chambers.

The term “valve” as used herein refers to a component of a pumpingsystem disposed in, or adjacent to, a fluid line or fluid flow pathwithin the system, which component is able to block the flow of a fluidtherethrough. Valves, which may be utilized in various aspects of theinvention, include, but are not limited to, ball valves, gate valves,needle valves, globe valves, solenoid-activated valves, mechanisms orcomponents for applying an external force to a fluid flow path so as toblock or occlude the flow path (for example, by pinching or collapsing alength of flexible tubing), and others, as would be apparent to those ofordinary skill in the art. Two or more chambers or regions of a pumpingsystem which are connected together by a fluid flow path including oneor more valves therein are able to be placed in fluid communication.“Able to be placed in fluid communication” as used herein refers tocomponents, regions, or chambers within a pumping system, whichcomponents, regions, or chambers are either connected in unrestrictedfluid communication or have at least one valve therebetween that can beselectively opened to place the components, regions, or chambers influid communication. Components, regions, or chambers connected togetherby a fluid flow path that includes no valves or obstructions therein aresaid to be in “unrestricted fluid communication” as used herein. Theterm “fluid communication” generally includes both unrestricted fluidcommunication and able to be placed in fluid communication.

In many pumping applications, e.g., pumping liquids to the body of apatient, it is critical to prevent gases, such as air, which may findtheir way into a pump chamber of the system from being pumped out (e.g.,pumped into the body of the patient). Certain embodiments of the presentinvention include methods and systems for detecting the presence of agas in an isolatable pump chamber. Such methods and systems may utilizepump chambers having at least one moveable surface, where, in someembodiments the moveable surface is a flexible membrane, which, in somesuch embodiments is elastic. The term “membrane” as used herein refersto a movable surface which comprises at least a portion of a wall of apump chamber. The term “flexible membrane” as used herein refers to amoveable surface having at least a portion that is movable by bendingand/or stretching when a force is applied thereto. A flexible membranewhich is “elastic” or an “elastic membrane” as used herein refers to aflexible membrane that provides a resistance to bending and/orstretching by an applied force, which resistance is proportional to anamount of the displacement/stretching of the membrane from anequilibrium configuration without such force applied. A force applied toan elastic membrane that displaces the membrane from a relaxedequilibrium condition will tend to create a stress in the membrane whichresists further displacement and creates a restoring force tending toreturn the membrane to its relaxed equilibrium condition. An“equilibrium condition” as used herein for elastic membranes or othermovable surfaces refers to the configuration of the membrane/surface ata condition where there are no applied forces tending to move ordisplace the membrane/surface from a stationary position. A “relaxedequilibrium condition” as used herein refers to an equilibrium conditionwherein a stress within a membrane/surface is at a minimum level allowedby the configuration of the pump chamber. For example, for a pumpchamber including an elastic membrane as a portion thereof, a relaxedequilibrium condition could be the configuration of the membrane at itsminimum level of strain (stretching) when forces on both sides of themembrane are essentially balanced and equal.

In one embodiment, a method for detecting the presence of a gas in anisolatable pump chamber having at least one moveable surface is used.The method involves isolating the pump chamber, which is at leastpartially filled with a liquid being pumped, for example by closing aninlet and an outlet valve in fluid communication with the pump chamber.The method of this embodiment further involves determining a measuredparameter related to the volume of the pump chamber with a predeterminedlevel of force is applied to a moveable surface of the pump chamber. Themethod further involves determining the measured parameter related tothe volume of the pump chamber again, except this time with a differentlevel of force applied to the moveable surface of the pump chamber. Themethod involves comparing the measured parameters determined at eachcondition of the pump chamber described, and detecting the presence of agas within the pump chamber based on the values of the measuredparameters.

This embodiment utilizes, at least in part, the compressibility of anygas within the pump chamber, as contrasted with the essentiallyincompressible nature of the liquid within the pump chamber, as a meansfor determining the presence of a gas. The presence of such gas in thepump chamber permits the movable surface to be able to undergo adisplacement in response to an applied force thereto owing to thecompressibility of the gas in the pump chamber. In some embodiments, themethod can involve the determination of a measured parameter related tothe volume of the pump chamber determined with at least twosubstantially differing levels of force applied to a moveable surface ofthe pump chamber. For example, a first determination of the measuredparameter related to the volume of the pump chamber at a first conditioncan be made with a positive force applied to the moveable surface of thepump chamber, such force tending to decrease the volume of the pumpchamber, and a second determination at a second condition can be madewith a negative (or lesser) force to the moveable surface of the pumpchamber, which force tending to increase the volume of the pump chamber.If the pump chamber is essentially completely filled with a liquid,because the liquid will be essentially incompressible, the measuredparameter related to the volume of the pump chamber measured with thepump chamber at a first condition (e.g., with the positive force appliedto the moveable surface of the pump chamber) will be nearly identical tothe value of the measured parameter related to the volume of the pumpchamber measured with the pump chamber at the second condition (e.g.,with a negative force applied to the moveable surface of the pumpchamber). In contrast, if the pump chamber also contains a quantity of agas, such as air, because the air is compressible, the measuredparameter related to the volume of the pump chamber measured at thefirst condition can differ from the value of the measured parametermeasured with the pump chamber at the second condition by an amountproportional to the quantity of gas within the pump chamber. In short,when a gas is present within the pump chamber, the volume of the pumpchamber measured utilizing a positive force applied to a moveablesurface thereof can be measurably different than the volume of the pumpchamber determined utilizing a negative force applied to a moveablesurface thereof. By comparing the measured parameters related to thevolume of the pump chamber determined at the first and second conditionsabove, it can be determined whether there is any gas present within thepump chamber and in some embodiments, roughly, the relative amount ofsuch gas.

A “measured parameter related to a volume” as used herein refers eitherto a measure of the volume itself or to a measured parameter determinedby the system that can be converted to the volume by arithmetic ormathematical transformations utilizing one or more additional parametersthat are either constant conversion factors or variables which are notfunctions of the volume (e.g., unit conversion factors, calibrationconstants, curve-fit parameters, etc.). In other words, in someembodiments of the invention, the volume of the pump chamber itself neednot be determined, but rather parameters from which the volume could bedetermined, which parameters are typically proportional to the volume,may be determined and compared. Depending on the embodiment, asdiscussed in more detail below, such measured parameters can include,for example, pressures and combinations of pressures, products ofpressures and volumes of components of the pumping system, acousticalsignals, temperatures, combinations of temperatures and pressures,values of linear displacement, etc. as apparent to those of ordinaryskill in the art. A “condition” as used above in the context of thedetermination of a measured parameter related to the volume of achamber, refers herein to a particular state of a pump chamber, or otherchamber in which a measured parameter is being determined, which stateis associated with at least one measurable parameter related to thevolume of the chamber with a particular level of force or range offorces being applied to an external surface of the chamber during thevolume measurement procedure.

As would be readily apparent to those of ordinary skill in the art fromthe disclosure provided herein, the method for determining the presenceof a gas in a pump chamber may be utilized and find application in awide variety of pumping systems known in the art, such pumping systemsincluding a force applicator for applying a variable, or selectable,force and/or range of forces to a moveable surface of the pump chamber.A “force applicator” as used herein in this context refers to acomponent of a pumping system that is able to apply a force to anexternal surface of a chamber within the system. Force applicators inpumping systems which may be utilized according to the inventioninclude, but are not limited to: moveable surfaces in contact with theexternal surface of the pump chamber (e.g. pistons, push rods, plungers,etc.), pressurized fluids in contact with the external surface of thepump chamber, magnetic or electrostatic fields that are able to exert aforce on the external surface of the pump chamber, and many others.

Pumping systems utilizing the inventive methods for determining thepresence of a gas in a pump chamber also preferably include a mechanismfor determining a measured parameter related to the volume of the pumpchamber with different levels of force or ranges of forces being appliedto a moveable external surface of the pump chamber. For example, apumping system which includes a moveable surface in contact with theexternal surface of the pump chamber can include a motor and linearactuator for moving the surface in contact with the pump chamber, so asto create a variable force on the surface of the pump chamber, and canfurther include a detector for measuring a linear displacement orposition of the moveable surface, which linear displacement or positioncan act as the measured parameter related to the volume of the pumpchamber. Similarly, systems which utilize a magnetic or electrostaticfield that is able to exert a force on the external surface of the pumpchamber can include detectors or measuring devices to determine eitherfield strengths and/or displacements of the external surface of the pumpchamber, which measurements can constitute a measured parameter relatedto the volume of the pump chamber. Other systems, and measurableparameters for determining the volume of the pump chamber foralternative systems may also be used.

One preferred embodiment of a pumping system able to employ theinventive method for detecting the presence of a gas in a pump chamberutilizes pressurized fluids in contact with a moveable, or flexible,surface of the pump chamber in order to apply a force to the surface.Preferred pumping systems according to the invention utilize fluidsources for providing a measuring fluid at different and selectablepressures, which fluid can be brought into contact with a moveable orflexible external surface of a pump chamber. As will be discussed inmore detail below, some preferred embodiments of pumping systemsutilizing measurement fluids for applying forces to moveable surfaces ofpump chambers employ pump chambers having a moveable surface comprised,at least in part, by an elastic flexible membrane. The term “fluidsource(s)” as used herein refers to one or more components of a pumpingsystem that alone, or in combination, are able to supply or withdraw aquantity of fluid to another component, or components, of the pumpingsystem with which they are, or are able to be placed, in fluidcommunication. As discussed below, examples include, but are not limitedto, pumps, compressors, pressurized or evacuated tanks, and combinationsthereof.

As discussed in more detail below, the fluids supplied by the fluidsources included in certain embodiments of pumping systems useful forpracticing the invention provide a measurement gas, most preferably air,but in other embodiments, can also provide one or more liquids. Suchfluids, which are provided by the fluid supply components of certainembodiments of the pumping systems according to the invention arehereinafter collectively referred to as “measurement fluids.”“Measurement fluids” (e.g., measurement gases or measurements liquids)as used herein refer to fluids which are used to determine a volume, ora measured parameter related to a volume of a volumetric containerwithin the pumping system, for example a pump chamber, or for otherpurposes within the pumping system, which, preferably, are not in fluidcommunication with a fluid being pumped or metered by a pump chamber ofthe system. The measurement fluid sources utilized by certain preferredembodiments of pumping systems according to the invention can compriseone or more components of a measurement fluid supply system that areconstructed and arranged to pressurize one or more components of thepumping system. “Constructed and arranged to pressurize” a component, asused herein, refers to a system containing the necessary sources offluid, together with the associated components (e.g., plumbing andpneumatic or other connections), which are necessary to enable thesystem to change the pressure of a fluid contained within the component.

One embodiment of a pumping system that utilizes a measurement gas foractuating a pump chamber to pump a liquid therethrough and for detectingthe presence of a gas in the pump chamber is shown schematically inFIG. 1. Pumping system 100 includes a fluid supply system 102 containinga fixed quantity of a measurement gas and a mechanism for changing thevolume of the measurement gas within the system.

Pumping system 100 includes a pump 104 comprising a substantially rigidcontainer 106 that includes a pump chamber 108 and a control chamber 110disposed therein. Pump chamber 108 and control chamber 110 arefluidically isolated (i.e., not able to be placed in fluidcommunication) from each other by a flexible membrane 112, disposedbetween the two chambers, such that pump chamber 108 is coupled tocontrol chamber 110 and in operative association therewith. Such amembrane may (as just one example) be constructed of medical gradepolyvinyl chloride.

“Substantially rigid” as used herein refers to a material, or acomponent constructed therefrom, that does not flex or movesubstantially under the application of forces applied by the pumpingsystem. A “control chamber” as used herein refers to a chamber of apumping system that is coupled to, or contains, a volumetric chamber,for example a pump chamber, for the purpose of exerting a force on thevolumetric chamber and, in preferred embodiments, for determining ameasured parameter related to the volume of the volumetric container.The term “coupled to” as used in this context with respect to chambersor other components of the pumping system, refers to the chambers orcomponents being attached to, or interconnected with, another componentof the pumping system, such that the other component is able to exert aforce on an external surface of the chamber or component to which it iscoupled.

Liquid to be pumped by pump system 100 enters pump chamber 108 via inletline 114 including an inlet valve 116 therein. Liquid can be pumped frompump chamber 108 to a desired downstream destination through outlet line118 including an outlet valve 120 therein.

Control chamber 110 includes a pressure measuring component 122 thereinfor determining the pressure of the measurement gas within the controlchamber. A “pressure measuring component” as used herein refers to adevice that is able to convert a fluid pressure into a measurable signalor parameter. Pressure measuring components that may be useful in thisembodiment include but are not limited to: transducers; pressure gauges;manometers; piezoresistive elements; and others as apparent to those ofordinary skill in the art.

Preferred embodiments of control chamber 110 of pumping system 100 alsoinclude a vent line 124 including a vent valve 126 therein. Controlchamber 110 is connected in fluid communication with a variable volumecylinder 128 via a measurement gas inlet line 130. Variable volumecylinder 128 which includes a piston 132 therein which is moved andactuated by motor 133 for compressing, or expanding the volume of themeasurement gas contained within the system.

Pumping system 100 also preferably contains a processor 134 which is inelectrical communication with the various valves, pressure transducers,motors, etc. of the system and is preferably configured to control suchcomponents according to a desired operating sequence or protocol.Reference to a processor being “configured” to perform certain tasksherein refers to such processor containing appropriate circuitry,programming, computer memory, electrical connections, and the like toperform a specified task. The processor may be implemented as a standardmicroprocessor with appropriate software, custom designed hardware, orany combination thereof. As discussed in more detail below, processor134, in addition to including control circuitry for operating variouscomponents of the system, also preferably includes a comparer that isconfigured to determine a measured parameter related to the volume ofpump chamber 108 and to detect the presence of any gas contained withinpump chamber 108 during operation of pump 104. A “comparer” as usedherein refers to a processor (e.g., with appropriate programming) orcircuit or component thereof that is able to compare the values of twoor more measured parameters or other parameters derived therefrom.

In embodiments where passing gas through the system is problematic, pumpchamber 108 is oriented in an essentially vertical configuration duringoperation such that inlet line 114 is disposed above outlet line 118.The above-described orientation is advantageous for preventing any gaswhich may be present in pump chamber 108 during operation from beingpumped from the pump chamber to a downstream destination through outletline 118. Instead, any gas contained within pump chamber 108 will tendto rise towards the top of the pump chamber, for example the regionadjacent to inlet port 136, and will be detected by the system, asdescribed in more detail below, before being pumped from the pumpchamber.

In some embodiments, pump chamber 108 includes the novel inclusion of aplurality of spacers 138 included therein. The spacers 138 function toprevent flexible membrane 112 from contacting an inner surface 140 ofthe pump chamber when the liquid contained within pump chamber 108 isbeing pumped through outlet line 118. During the pump stroke, themaximum displacement of flexible membrane 112 which is permitted byspacers 138 is shown in FIG. 1 by dashed line 142. It can be seen thateven with flexible membrane 112 at its maximum displacement into pumpchamber 108, as defined by dashed line 142, spacers 138 create a deadspace 144 to contain any gas which may be present in pump chamber 108,thus inhibiting the gas from being pumped through the pump chamber.Spacers 138, in combination with the vertical orientation of pumpchamber 108, also serve to assist any gas present in pump chamber 108 torise to the top of the pump chamber so that it may more easily be purgedfrom the pump chamber, as described in more detail below.

Pump chamber 108 of pumping system 100 is essentially defined by asubstantially rigid wall 145 (e.g., made of a rigid plastic such as apolyacrylate) having a flexible membrane 112 disposed over the wall,thus forming a volumetric chamber. An alternative embodiment forproviding a pump chamber and a control chamber is shown in FIG. 2. Pump152 of pumping system 150 includes a pump chamber 154 which comprises anessentially flexible container 156 disposed within a substantially rigidenclosure 158 having an interior volume surrounding pump chamber 154which comprises a control chamber 160. In other embodiments (not shown),the pump chamber may be differently configured or disposed within thecontrol chamber and may include substantially rigid, but moveablesurfaces, as opposed to the flexible surfaces of pumping systems 100 and150 described above.

One embodiment of a method for operating the pumping system 100 shown inFIG. 1 for pumping a liquid with pump chamber 108, and for detecting thepresence of a gas in pump chamber 108, is shown in detail in the flowcharts of FIGS. 3 a-3 c.

Referring to FIG. 3 a, an exemplary pump cycle utilizing pumping system100 will be described. The pump cycle illustrated utilizes changes indisplacement of the piston to change the pressure of a measurement fluidwithin the system in order to apply selected forces to membrane 112 forpumping and air detection. The embodiment illustrated also utilizes anequation of state (e.g. the ideal gas law) in determining pump chambervolumes from measured or known values of pressure and volume.

For embodiments employing a protocol for detecting air/gas where pumpand/or control chamber volumes are determined, at least in part, frommeasured pressures by utilizing an equation of state describing thepressure-volume behavior of a measurement gas, the pump chamberpreferably includes a movable surface which comprises an elasticmembrane. The restoring force of the elastic membrane, when stretched ordisplaced from a relaxed equilibrium condition, enables the pressure oneach side of the membrane (i.e. in the pump chamber and control chamber)to be different, where the degree of difference in the pressures, andthe resistance to further displacement/stretching (stress/elastic energystored in the membrane), is a function of the degree of stretch ordisplacement from the relaxed equilibrium condition of the membrane. Insuch embodiments, it is also preferred that the measurement gaspressures applied to the elastic membrane during the determination ofpump/control chamber volumes at the first and second conditions ofapplied force for detecting air/gas in the pump chamber discussed above,tend to stretch the elastic membrane (if air/gas is present in the pumpchamber), from its equilibrium configuration before the pressure isapplied, by a different extent for each condition, so that the stress inthe membrane and its resistance to further displacement in response to agiven level of applied pressure will be different for the first andsecond condition (or in other words, the force/displacement response ofthe elastic membrane for the first and second conditions will beasymmetrical). In such embodiments, the difference in the pressure inthe control chamber versus the pressure in the pump chamber, at anequilibrium condition, will be different for the first condition ofapplied pressure versus the second condition of applied pressure. Insuch embodiments, without being tied to any particular physicalmechanism, it is believed that the different level of stress and strainof the elastic membrane during measurements of pump/control volumedetermined at the first and second conditions above create, at least inpart, deviations in the pressure-volume behavior of the measurement gasfrom that predicted for each condition by the equation of state, whichdeviations can create and/or enhance a difference in the volume of thepump/control chamber determined for each condition by using the equationof state.

In some embodiments, one way to achieve or enhance such asymmetry in theresponse of the elastic membrane to the applied measurement gaspressures utilized during volume determinations for gas detection is toperform the volume determination steps when the pump chamber flexibleelastic membrane has already been stretched, from the configuration ithas at a relaxed equilibrium condition, with essentially equal fluidpressures on each side of the membrane, before the application ofpressurized measurement gas to the membrane for the purpose of volumemeasurement. This can be accomplished, for example, by performing thevolume determinations related to air/gas detection after filling thepump chamber with sufficient liquid so that the elastic membrane is atleast somewhat stretched, and preferably substantially stretched, bydisplacement of the membrane in the direction of the control chamber,and by using a positive measurement gas pressure during volumemeasurement at the first condition and a negative measurement gaspressure during volume measurement at the second condition (or visversa). Such a condition of displacement of elastic membrane 112 forpump 104 is illustrated in FIG. 4, which shows pump chamber 108 afterfilling with a liquid 220 to be pumped and immediately before volumetricmeasurements performed (as described below) for detecting the presenceof a gas 222 in the pump chamber. In alternative embodiments the desiredasymmetry in the response of the elastic membrane during volumedeterminations involved in air/gas detection could also be achieved byutilizing levels of measurement gas pressures applied to the elasticmembrane for volumetric determinations performed at the first and secondconditions of measurement that are selected to impart a different, andpreferably substantially different degree of elastic stretch to themembrane. While preferred embodiments of pump chambers for use whenutilizing an equation of state based procedure for calculatingpump/control chamber volumes include a moveable surface at leastpartially comprised of an elastic membrane, in alternative embodiments,non-elastic movable surfaces could potentially be used so long as themeasurement fluid pressures applied to the surface during volumemeasurement at the first condition and second condition create adifferent levels of stress in the surface and different differences inthe equilibrium pressures within the control and pump chamber. Suchembodiments could, for example, utilize a non-elastic movable surface orflacid membrane, where measurement fluid pressures applied during thefirst condition of volume determination tend to move thesurface/membrane (if a gas is present in the pump chamber) to itsmaximum allowed displacement so that the surface is no longer free tomove in response to the applied force, a stress is created in thesurface/membrane, and a pressure difference exists between the pump andcontrol chambers. Measurement of volume at a second condition for suchembodiments could apply a different measurement fluid pressure to thesurface, which pressure tends to move the surface/membrane (if a gas ispresent in the pump chamber) to reduce or substantially eliminate thestress within the surface/membrane so that at equilibrium, thedifference in pressure in the pump and control chambers is reduced oressentially eliminated.

Referring again to the protocol of FIG. 3, initially, it will be assumedthat pump chamber 108 has been emptied, and that elastic membrane 112 isextending into pump chamber 108 at its maximum allowable displacementdefined by line 142. Piston 132 is assumed to be at its far leftposition of travel (shown as position 1 in FIG. 1). Referring to FIG. 3a, step 1 (170) involves initializing the system so that all valves areclosed and piston 132 and flexible membrane 112 are in the positionsdescribed above.

Step 2 (172) involves filling the pump chamber 108 with a liquid to bepumped. The step involves first opening inlet valve 116, then actuatingmotor 133 so as to move piston 132 to position 3 shown in FIG. 1,thereby increasing the volume of pump chamber 108 by an amount definedas ΔV. Then, inlet valve 116 is closed in order to isolate pump chamber108. Step 3 (174) of the exemplary pumping cycle involves a series ofsubsteps for determining the volume of control chamber 110 and/or pumpchamber 108 and for detecting the presence of any gas contained withinpump chamber 108. Step 3 (174) is described in greater detail in FIG. 3b.

Referring again to FIG. 3 a, step 4 (208) of the pumping cycle involvesdelivering the liquid contained in pump chamber 108. First, outlet valve120 is opened. Motor 134 is then actuated to move piston 132 fromposition 3 to position 1, thereby delivering a volume of fluid ΔV.Outlet valve 120 is then closed in order to isolate pump chamber 108. Insome embodiments, where the accuracy of determining the volume deliveredby pump chamber 108 is critical, the volume of pump chamber 108 afterstep 4 (208) may be determined (e.g., by repeating substeps 1-4 (176,178, 180, 182) of the volume calculation and air detection subcycle ofFIG. 3 b described below). In which case, the volume delivered for theabove described pump stroke can be determined by taking a difference inthe volume of pump chamber 108 determined in step 3 (174) and in step 5(210). Finally, if multiple pump strokes are desired, the entire pumpcycle of FIG. 3 a may be repeated.

Referring to FIG. 3 b-3 c, one embodiment of a volume calculation andgas detection method, shown at step 3 (174) of FIG. 3 a, is shown.Substep 1 (176) of subcycle 174 involves measuring the pressure P₁ ofthe measurement gas in control chamber 110 with pressure transducer 122and recording or storing the pressure with processor 134. In substep 2(178) piston 132 is moved from position 3 to position 1 thereby reducingthe volume of the measurement gas contained within the system by ΔV. Insubstep 3 (180) the pressure of the measurement gas in control chamber110 is measured again and recorded as P₂. It will be appreciated that P₂will be greater than P₁ due to the compression of measurement gas withinthe system. The volume of fluid contained in pump chamber 108 is thendetermined in substep 4 (182), with the pump chamber at this firstcondition, using an appropriate equation of state for the measurementfluid being utilized. In the case of a measurement gas, such as air, forsystems utilizing pumping pressures which are relatively low (typicalpumping pressures utilized by pumping systems according to the inventionrange from abut −14 psig to about 15 psig) the ideal gas law can beemployed. Recognizing that no measurement gas was added to or removedfrom the system, and utilizing the ideal gas law combined withconservation of mass, the volume of fluid contained in pump chamber 108is determined by:

$\begin{matrix}{V_{F} = {V_{T} - \frac{P_{2}\Delta \; V}{P_{2} - P_{1}}}} & (1)\end{matrix}$

Equation 1 assumes that any temperatures changes or differences causedby changing the volume of measurement gas are minimal and that thesystem is essentially isothermal. It will be appreciated that forsystems where temperature changes may be significant, the temperaturedependence of the measurement fluid, as defined by the equation of statebeing used, may be incorporated into the volume calculation of substep 4(182) in a straightforward fashion, as apparent to those of ordinaryskill in the art. V_(F) in equation 1 refers to the internal volume ofpump chamber 108 and V_(T) refers to the known total volume of thesystem including pump chamber 108, control chamber 110, and the volumescontained within measurement fluid inlet line 130 and cylinder 128.

The remaining substeps of the volume calculation subcycle 174 involveredetermining the volume of the pump chamber 108 at a differentcondition and comparing the volumes determined at the first and secondconditions. In substep 5 (184) of FIG. 3 b, control chamber vent valve126 is opened to equilibrate the pressure in control chamber 110 withthe surrounding atmosphere. Vent valve 126 is then closed. A newpressure P₁ is measured with transducer 122 in control chamber 110 insubstep 6 (186). In substep 7 (188) piston 132 is moved from position 1to position 3 thereby increasing the volume of measurement gas withinthe system by ΔV. In substep 8 (190) the new pressure P₂ in controlchamber 110, which pressure will be below atmospheric pressure, ismeasured and recorded. In substep 9 (200) the volume of pump chamber 108V_(F) is calculated as described above in substep 4 (182). Substep 10(202) involves determining the difference between V_(F) determined insubstep 4 (182) and V_(F) determined in substep 9 (200) and taking anabsolute value of the difference. In substep 11 (204), shown in FIG. 3c, the above difference is compared to a predetermined limit that isproportional to a maximum allowable quantity of air or other gas whichcan be present in pump chamber 108 during operation. The predeterminedlimit is typically determined empirically, as discussed below, andchosen such that air volume exceeding dead space 144 volume will alsoexceed the predetermined limit. If the difference exceeds thepredetermined limit the processor 134 will create an alarm condition andinitiate an air purge, as described in more detail below.

If the difference in measured volumes is less than the allowable limit(204), the system will proceed to pump the liquid contained in pumpchamber 108. In substep 12 (206) the system opens control chamber ventvalve 126 in order to equilibrate the pressure in control chamber 110and the surrounding atmosphere, and then closes vent valve 126. Pumpingsystem 100 is now in condition to deliver the liquid contained in pumpchamber 108.

As described above, the measured volumes at the two different conditionscan be compared to detect the presence of gas in the pump chamber. Ifthe presence of a gas is detected in the pump chamber and is ofsufficient quantity to cause the system to set off an alarm, asdescribed above in substep 11 (204) FIG. 3 c, instead of proceeding todeliver the fluid to a desired downstream destination as describedabove, the pumping system 100 will instead initiate an air purge. Duringthe air purge, instead of outlet valve 120 being opened while fluid isbeing pumped from pump chamber 108, inlet valve 116 is opened, and thefluid, including any gas in the pump chamber, is pumped from the pumpchamber through inlet line 114 to a safe purge destination.

It should be appreciated that while the above described example of apump stroke cycle for pumping system 100 was described as being fullycontrolled, and regulated by a processor, the method could equivalentlybe performed under manual operator control without utilizing such aprocessor or by using any other mechanism to control the operation. Inaddition, while the above described methods involve an essentially idealgas as a measuring fluid, other embodiments of the invention may utilizenon-ideal measurement gases, or liquids as measurement fluids. When suchalternative measurement fluids are used, the ideal gas law may no longerbe an appropriate equation of state to utilize for determiningvolumetric measurements but instead an equation of state appropriate forthe measurement fluid being used may be utilized. In addition, asdiscussed earlier, a variety of other techniques for measuring thevolume contained in a volumetric container can be used to determine ameasured parameter related to the volume of a pump chamber having amovable surface or flexible membrane at a first and second condition ofapplied force, such alternative means of volumetric measurement beingapparent based on the disclosure herein and are within the scope of thepresent invention. In addition, also as discussed previously, theskilled practitioner will envision many alternative mechanisms forapplying a variable level of force to a moveable wall, for exampleflexible elastic membrane 112, or other movable wall configuration, of apump chamber, which can be substituted for the pressurized gas pumpdrive system 230 described in FIG. 1. It should also be emphasized thatthe particular steps described as part of the exemplary pump cyclemethods described herein may be performed in a different sequence, andcertain steps may be substituted or eliminated, without effecting theoverall performance of the methods. For example, when detecting thepresence of a gas in the pump chamber, instead of applying a positivepressure to the flexible membrane of the pump chamber to calculate afirst volume followed by applying a negative pressure to the flexiblemembrane of the pump chamber to calculate a second volume, these stepscould easily be interchanged or both pressures may be positive ornegative, so long as they differ by a sufficient amount to enable thedetection of gas in the pump chamber.

FIG. 5 shows a pumping system 300 utilizing an alternative pump drivesystem 302 including a measurement fluid supply system 304 which is aconstant volume system. Fluid supply 304 is able to apply a force toflexible membrane 112 of pump chamber 108 by changing the quantity of ameasurement gas contained within constant volume fluid supply system304. Pump drive system 302 of pumping system 300 includes a controlchamber 110 which is connected via measurement gas inlet line 306 to areference chamber 308 having a known volume. Measurement gas is suppliedto reference chamber 308 and control chamber 110 via pump 312. Pumpingsystem 300 also includes a processor 324, similar to that describedpreviously for pumping system 100 shown in FIG. 1, which is configuredto control the operation of the various components of the system andperform determinations of measured parameters related to the volume ofpump chamber 108, as described in more detail below.

An exemplary embodiment of a pump stroke cycle, including the detectionof a gas in pump chamber 108 utilizing the ideal gas law in determiningpump chamber volumes, which can be utilized for operating pumping system300 is described in FIGS. 6 a-6 c. Referring to FIG. 6 a, initially, itis assumed that pump chamber 108 has been emptied and flexible membrane112, preferably an elastic membrane as previously discussed in thecontext of system 100 of FIG. 1, is displaced into pump chamber 108 asdescribed previously with regard to FIG. 3 a. In addition, in theinitial state of the system in step 1 (350) it is assumed that allvalves of the system are closed. Step 2 (352) of the method involvesfilling pump chamber 108 with a liquid through inlet line 114 and inletvalve 116. The step involves first opening valve 314 located on line 310between reference chamber 308 and pump compressor 312, and operatingpump 312 to create a desired negative pressure in reference chamber 308,as measured by pressure transducer 316. Next, valve 318 on line 306 andinlet valve 116 are opened. The operation of pump 312 can bediscontinued when pump chamber 108 has filled with liquid to a desiredextent. In step 3 (354) of the method, pump chamber 108 and controlchamber 110 are isolated by closing inlet valve 116 and valve 318.

Step 4 (356) comprises a volume calculation and air detection subcycledescribed below in more detail with reference to FIG. 6 b. The liquidcontained in pump chamber 108 is delivered through outlet line 118 instep 5 (374). Step 5 (374) involves opening valve 314, operating pump312 to create a desired positive pressure in reference chamber 308,opening valves 318 and outlet valve 120, and allowing the liquidcontained in pump chamber 108 to flow through outlet line 118 until adesired quantity of liquid has been delivered. At which point, in step 6(376), outlet valve 120 is closed, so as to isolate pump chamber 108,and valve 318 is closed to isolate control chamber 110. In step 7 (378)the final volume of pump chamber 108 is determined (e.g., byre-performing substeps 1-6 of FIG. 6 b described below and calculating afinal volume V_(F2)). The volume delivered by pump chamber 108 duringthe pump stroke is calculated in step 8 (380) by taking a differencebetween the pump chamber volume V_(F1) determined in step 4 (356) andthe pump chamber volume V_(F2) determined in step 7 (378). Forembodiments involving delivery of liquids via multiple pump strokecycles, the steps described in FIG. 6 a can be repeated.

FIG. 6 b shows one embodiment of a method for determining gas volume inthe method of FIG. 6 a step 4 (356). Substep 1 (358) comprises anoptional step whereby the pressure in control chamber 110 isequilibrated to the atmosphere by opening an optional vent valve 320located on optional vent line 322 connected to control chamber 110.After equilibration with the atmosphere, vent valve 320 is closed. Insubstep 2 (360) pressure P_(C1) in control chamber 110 is measured withpressure transducer 122 and stored by processor 324. In substep 3 (362),pump 312 is operated so as to increase the pressure P_(R) in referencechamber 308 to a value P_(R1) that is greater than P_(C1) and alsogreater than atmospheric pressure. After such pressure in referencechamber 308 is obtained, the operation of pump 312 is discontinued,valve 314 is closed, and pressure P_(R1) in reference chamber 308 ismeasured with pressure transducer 316 and stored by processor 324.

Substep 4 (364) involves allowing a quantity of measurement gas to beexchanged between control chamber 110 and reference chamber 308. Thiscan be accomplished by opening and, optionally, closing valve 318. Ifdesired, valve 318 may be opened for a sufficient time to allow thepressure in control chamber 110 and reference chamber 308 to equilibrateto a common value. For embodiments where the pressures in controlchamber 110 and reference chamber 308 are allowed to equilibrate insubstep 4, the system can compare the pressure signals obtained frompressure transducer 122 and pressure transducer 316 and can create analarm condition indicating a system fault if the pressures do notessentially agree.

In substep 5 (366) the system determines pressure P_(C2) in controlchamber 110 and P_(R2) in reference chamber 308 and records thepressures (P_(C2) and P_(R2) should be essentially the same if thepressures in control chamber 110 and reference chamber 308 were allowedto equilibrate in substep 4 above).

In substep 6 (368) the volume of the control chamber 110, (which alsoincludes the volume of line 306 up to valve 318 and line 322 up to valve320) is determined at this first set of conditions of measurement (or“first condition” as used herein) from the known volume of referencechamber 308 and the pressures determined above utilizing the ideal gaslaw equation of state and conservation of mass for the measurement gasexchanged during substep 4 (364) above. As described for the previousembodiment, equations of state other than the ideal gas law may be usedfor measurement fluids which do not simulate ideal gas behavior. Also,as before, the system is assumed to be isothermal, specifically, thetemperature in reference chamber 308 is assumed to be equal to thetemperature in control chamber 110 during pressurization and gasexchange. The volume of the control chamber described above V_(C) isdetermined by:

$\begin{matrix}{V_{C} = \frac{( {P_{R\; 1} - P_{R\; 2}} )V_{R}}{( {P_{C\; 2} - P_{C\; 1}} )}} & (2)\end{matrix}$

where V_(R) is the known volume of reference chamber 308. The volume offluid in pump chamber 108 may be explicitly determined, if desired, bysubtracting V_(C) from V_(T), which is the known total volume of pumpchamber 108 and control chamber 110.

In substep 7 (370) and substep 8 (372) the presence of any gas containedin pump chamber 108 is determined. In substep 7 (370), substeps 1-6(358, 360, 362, 364, 366, 368) described above are repeated, except thatin substep 2, pump 312 is operated so as to decrease the pressure inreference chamber 308 to a value lower than that of the pressure incontrol chamber 110 and atmospheric pressure. In substep 8 (372) theprocessor determines the difference between the volume of pump chamber108 determined in substep 7 (370) (i.e. the volume determined at thesecond set of measurement conditions or “second condition” as usedherein) and the volume of pump chamber 108 determined in substep 6(368).

As shown in FIG. 6 c, the value of the difference in the calculatedvolumes is compared to a predetermined threshold limit (step 390), andif the value exceeds the limit processor 324 creates an alarm conditionand initiates an air purge (step 392), similar to that describedpreviously. If the system fails to detect any gas in pump chamber 108(i.e., the difference in the measure volumes is below the thresholdlimit) the system will proceed to deliver liquid contained in pumpchamber 108, as described in more detail in FIG. 6 a.

An alternative embodiment to the pump system 300 shown in FIG. 5, whichalso utilizes a pump drive system including a fluid supply system havinga constant known volume, is shown in FIG. 7. A pumping system 400 havinga pump drive system 402 including a fluid supply system 404 including areference chamber 406 having a known volume. As opposed to system 300shown in FIG. 5, where the measurement gas was supplied to referencechamber 308 by a pump 312, in pumping system 400, measurement gas issupplied to reference chamber 406 via a positive pressure storage tank408 and a negative pressure storage tank 410. Positive pressure storagetank 408 is connected to reference chamber 406 via line 412 containing avalve 414 therein. Negative pressure tank 410 is connected to referencechamber 406 via line 416 containing a valve 418 therein. In preferredembodiments, positive pressure tank 408 and negative pressure tank 410each include pressure transducers 420 and 422 for continuouslymonitoring the pressure of a measurement gas contained therein. Asillustrated in the figure, fluid supply system 404 of pumping system 400is a completely closed system wherein measurement gas is containedwithin the system without additional quantities of measurement gas beingadded to or removed from the system during the pump cycle. However, inalternative embodiments, the system can include one or more lines forfluid communication with the environment for venting or other purposes.In one such alternative embodiment, instead of pump 424 creating apressure difference between tanks 408 and 410 by pumping measurement gasfrom tank 410 to 408, the pump could pump air from the surroundings totank 408 and could pump air from tank 410 to the surroundings to createthe pressure difference.

Before the beginning of a pump cycle which utilizes pumping system 400,a pressure differential between positive tank 408 and negative tank 410is established by opening valves 421 and 423 and operating pump 424 tomove measurement gas from negative tank 410 to positive tank 408. Thepump cycle and volume measurement cycle utilizing system 400 is similarto that described for system 300 of FIG. 5, except that in order tocreate a positive pressure of measurement gas in reference chamber 406and control chamber 110 and in order to create a different (in thisexample, negative) pressure in reference chamber 406 and control chamber110 the chambers are placed in fluid communication with positive tank408 and negative tank 410 respectively, instead of establishing thepressures by utilizing a pump.

Pumping system 400 enables a more constant and controllable pressure tobe applied to control chamber 110 during the filling and emptying ofpump chamber 108, as compared to pump system 300 shown in FIG. 5.Preferably, positive tank 408 and negative tank 410 have internalvolumes that are substantially greater than the internal volume ofreference chamber 406 and control chamber 110. In preferred embodiments,positive tank 408 and negative tank 410 have volumes that aresufficiently greater than those of reference chamber 406 and controlchamber 110 so that the pressure of measurement gas in tanks 408 and 410remain essentially constant throughout the pump cycle. Typically, tanks408 and 410 will be at least 10 times larger, and are preferably atleast 20 times larger in volume than reference chambers 406 and controlchamber 110. In general, for pumping systems utilizing a control chamberand a reference chamber (for example the systems shown in FIG. 5 andFIG. 7 and described below in FIG. 8) the control chamber preferably hasa volume similar to or on the same order of magnitude as the volume ofthe pump chamber, and the reference chamber has a volume that is fromabout 1-10 times that of the control chamber.

It should be appreciated that the particular ways in which the varioustanks, valves, pumps, and chambers of the various pumping systemsdescribed herein are arranged, configured, and interconnected can bevaried considerably without changing the overall performance oroperation of the pump drive system. A variety of alternativeconfigurations for the pumping systems described herein have beenpreviously described in U.S. Pat. Nos. 4,778,451, 4,808,161, 4,826,482,4,976,162, 5,088,515, and 5,178,182, each of which is commonly owned andwhich are incorporated herein by reference in its entirety.

A preferred arrangement of components for providing a pump drive systemaccording to the invention is shown in FIG. 8. Pumping system 500includes a pump 104 including a pump chamber 108 separated from acontrol chamber 110 by a flexible membrane 112 disposed therebetween,similar to that described previously. Pumping system 500 includes a pumpdrive system 502 including a fluid supply system 504 connected in fluidcommunication with control chamber 110. Pump drive system 502 includes aprocessor 506 configured for controlling the various components of thesystem for pumping a liquid with pump chamber 108, and including acomparer for determining the presence of a gas in pump chamber 108 frommeasured parameters related to the volume of pump chamber 108, asdescribed previously. Fluid supply system 504 includes a positivepressure source comprising a positive pressure tank 508 with ameasurement gas having a positive pressure contained therein. Positivepressure tank 508 includes a pressure transducer 510 configured tomeasure the pressure of the measurement gas and send a signal toprocessor 506. Fluid supply system 504 also includes a negative pressuresource comprising a negative pressure tank 512 having a measurement gasat a negative pressure contained therein. Negative pressure tank 512includes a pressure transducer 514 for measuring the pressure of ameasurement gas contained therein.

Fluid supply system 504 also contains a pump 516 positioned andconfigured to pump measurement gas from negative tank 512 through line518, valve 520, valve 522 and line 524 to positive pressure tank 508, soas to establish a pressure difference between the measurement gascontained in positive pressure tank 508 and negative pressure tank 512.Positive pressure tank 508 has an outlet line 526 and negative pressuretank 512 has an outlet line 528, each of which lines are in fluidcommunication with a switch valve 530. The outlet of switch valve 530 isable to be placed in fluid communication with both control chamber 110and reference chamber 532 of the system. Switch valve 530 is preferablya solenoid-operated three-way type valve which is controlled byprocessor 506 so that in a first position, positive pressure tank 508 isplaced in fluid communication with control chamber 110 and/or referencechamber 532, and in a second position negative pressure tank 512 isplaced in fluid communication with control chamber 110 and/or referencechamber 532.

Outlet line 534 from switch valve 530 includes a variable-sized orificevalve 536 therein, which valve comprises, in preferred embodiments, avalve having an orifice for fluid flow therethrough, where the size ofthe orifice is selectively adjustable over an essentially continuousrange of values in order to control a flow rate of fluid therethrough.The size of the orifice in variable size orifice valve 536 iscontrolled, in preferred embodiments, by processor 506 in order toselectively vary the pressure of the measurement gas downstream ofvariable size orifice valve 536. Variable size orifice valves for use inthe invention are known in the art and have been utilized for otherpurposes. Such valves are available, for example, from Parker HannifinCorp., Pneutronics Division.

One embodiment of the present invention involves the novel incorporationof such a variable size orifice valve in a fluid supply system formeasuring the volume of a volumetric chamber and, in some embodiments,for providing a pressurized fluid in contact with the moveable surfaceof a pump chamber.

The outlet of variable size orifice valve 536 is in fluid communicationwith measurement fluid inlet line 538, which provides measurement gas tocontrol chamber 110. The outlet of variable size orifice valve 536 isalso in fluid communication with valve 540 on inlet line 542 ofreference chamber 532. Reference chamber 532, in preferred embodiments,also includes a vent line 544 through which measurement gas can bevented to the atmosphere by opening valve 546. Reference chamber 532also includes a pressure transducer 548 in fluid communicationtherewith, which measures the pressure of a measurement gas in thereference chamber.

One embodiment of a method for operating pumping system 500 is shown inFIGS. 9 a-9 c. The preferred pump stroke cycle includes steps forfilling and dispensing a liquid from pump chamber 108, as well as stepsfor determining the volume of a volumetric container using the ideal gaslaw equation of state and conservation of mass, so as to determine avolume of liquid pumped and to detect the presence of any gas in pumpchamber 108. As above, it is assumed initially that pump chamber 108 hasbeen emptied of liquid and that flexible membrane 112, preferably anelastic membrane when, as here, pump chamber volumes are determinedusing the ideal gas law or other equation of state (as previouslydiscussed), is extending to the maximum permissible extent allowed byspacers 138 into pump chamber 108. Step 1 (600) involves initializingthe system. The initialization of the system involves opening valves 520and 522 and operating pump 516 to create a desired pressure ofmeasurement gas in positive pressure tank 508 and negative pressure tank512, followed by discontinuing the operation of pump 516 and closingvalves 520 and 522. It is also assumed as an initial condition that allvalves of the system are closed and that switch valve 530 is positionedso that its outlet is in fluid communication with positive pressure tank508.

Step 2 (602) involves filling pump chamber 108 with liquid through inletline 114 and inlet valve 116. First, switch valve 530 is positioned toselect negative pressure tank 512. Next, inlet valve 116 is opened andvariable size orifice valve 536 is opened until pump chamber 108 hasfilled with liquid. In preferred embodiments, variable size orificevalve 536 is also selectively controlled during filling so as to providean essentially constant negative pressure in control chamber 110, asdescribed in more detail below. As will also be described in more detailbelow, the ability to vary the pressure in control chamber 110 viacontrol of variable size orifice valve 536 enables system 500 to detectwhen flexible membrane 112 is distended into control chamber 110 to itsmaximum permissible extent indicating that pump chamber 108 iscompletely full of liquid. Thus, in preferred embodiments, system 500can detect when pump 104 has reached the end of a stroke, either in thefilling or emptying of pump chamber 108. This end of stroke detectionmethod of preferred embodiments for operating pump system 500 isdescribed in more detail below.

In step 3 (604) pump chamber 108 and control chamber 110 are isolated byclosing inlet valve 116 and variable size orifice valve 536respectively. Step 4 (606) comprises a subcycle which determines thevolume of the volumetric container comprising pump chamber 108 and/orthe volumetric container comprising control chamber 110, and determinesthe presence of any gas in pump chamber 108 utilizing the determinedvolumes. The various substeps of step 4 (606) are outlined in detail inFIGS. 9 b and 9 c.

Referring to FIG. 9 b, substep 1 (608), which is optional, involvesequilibrating the pressure in control chamber 110 and reference chamber532 with the atmosphere by opening valve 540 and valve 546 in order tovent the control chamber and the reference chamber through vent line544. Substep 2 (610) involves positioning switch valve 530 to selectpositive pressure supply tank 508, and opening variable size orificevalve 536 in order to pressurize control chamber 110. In someembodiments, variable size orifice valve 536 can be opened for asufficient period of time so that the pressure of measurement gas inpositive pressure supply tank 508 in control chamber 110 is allowed toequilibrate. In such embodiments, the pressure measured by transducer122 on control chamber 110 should be essentially the same as thatmeasured with pressure transducer 510 on the positive pressure tank. Ifthese pressures do not agree, processor 506 can be configured toindicate that there is a system fault and can shut down operation of thesystem. After pressurizing control chamber 110, variable size orificevalve 536 is closed and the measured pressure P_(CI) in control chamber110 is recorded. In substep 3 (612) the pressure P_(R1) in referencechamber 532, as measured with pressure transducer 548 (which will bedifferent from that in control chamber 110) is stored by processor 506.

Substep 4 (614) involves allowing for measurement gas exchange betweencontrol chamber 110 and reference chamber 532. The gas exchange isenabled by opening and, optionally, closing valve 540. In someembodiments, valve 540 may be opened for a sufficient period of time toequilibrate the pressures in reference chamber 532 and control chamber110 to essentially the same value. For such embodiments, it should beappreciated that pressure transducer 122 in fluid communication withcontrol chamber 110 is optional since the measurement gas pressures incontrol chamber 110 can be determined, for various steps of the method,with pressure transducers 548, 510, or 514. In substep 5 (616), afterallowing gas exchange, pressure P_(C2) and P_(R2) in control chamber 110and reference chamber 532 respectively are measured and stored byprocessor 506. The volume V_(C) of the control chamber and, optionally,the volume V_(F) of pump chamber 108 at this first condition can becalculated from the known volume Y_(R) of reference chamber 532 and theabove-measured pressures utilizing the ideal gas equation of state andconservation of mass, as described previously, from equation 2 shownpreviously.

In order to detect the presence of any gas in pump chamber 108, insubstep 7 (620), substeps 1-6 (608, 610, 612, 614, 616, 618) arerepeated as described above except that in substep 2 (610) switch valve530 is positioned to select negative pressure supply tank 512. Insubstep 8 (622) processor 506 determines an absolute value of thedifference between volume measurements determined in substep 7 (620)(i.e. at the second condition) and substep 6 (618) above and, as shownin FIG. 9 c, compares this difference to a predetermined permissiblelimit and creates an alarm condition and initiates an air purge frompump chamber 108, in a manner substantially similar to that previouslydescribed, if the value exceeds the limit. If the value does not exceedthe predetermined limit, the system proceeds to deliver the liquid inpump chamber 108, as described in FIG. 9 a, steps 5-7.

Referring again to FIG. 9 a, in step 5 (624), liquid is delivered frompump chamber 108 by, optionally, opening valves 546 and 540 to ventcontrol chamber 110, followed by closing valves 540 and 546, positioningswitch valve 530 to select positive pressure tank 508, and openingoutlet valve 120 on outlet line 118 of pump chamber 108 while openingand controlling the orifice size of variable size orifice valve 536 toyield a desired pressure in control chamber 110 for pumping the liquidfrom the pump chamber. In preferred embodiments, variable size orificevalve 536 is controlled by processor 506 to maintain the pumpingpressure in control chamber 110 at a desired value during the pumpchamber emptying stroke. In such embodiments, processor 506 preferablyincludes a controller, for example a PID closed loop control system,which allows the processor to selectively change the size of the orificewithin the variable size orifice valve 536 based, at least in part, on adifference between a pressure measured within control chamber 110 bytransducer 122, and a desired predetermined pumping pressure. Asdiscussed above in the context of filling pump chamber 108, pumpingsystem 500 also preferably includes a method for controlling variablesize orifice valve 536 so that the system is able to determine whenflexible membrane 112 has stopped moving into pump chamber 108indicating that liquid flowing from pump chamber 108 has stopped. Thisend of stroke detection method is described in more detail below. Aftera desired quantity of fluid has been delivered from pump chamber 108 orafter an end of stroke condition has been determined as discussed above,outlet valve 120 downstream of pump chamber 108 is closed and,optionally, variable size orifice valve 536 is closed in order toisolate the pump chamber and control chamber.

Step 6 (626) of the pump cycle involves repeating the volume calculationroutine by re-performing substeps 1-6 (608, 610, 612, 614, 616, 618)shown in FIG. 9 b to calculate a final volume V_(F2) of pump chamber 108after delivery of the liquid. Finally, in step 7 (628) the volumedelivered by pump 104 during the pump cycle ΔV can be determined bytaking a difference in the pump chamber or control chamber volumedetermined after filling pump chamber 108 (determined in step 4) and thevolume determined after pumping the liquid from pump chamber 108(determined in step 6). If desired, a new pump cycle can be initiated byrepeating the steps outlined in FIG. 9 a.

The flow rate of the liquid delivered from the pump chamber for eachpump stroke will be a function of the force applied to the flexiblemembrane of the pump chamber during the filling steps and delivery stepsdiscussed above, and a function of the upstream and downstream liquidpressures in fluid communication with the pump chamber inlet line andoutlet line respectively during filling and delivery. Typically, theforces applied to the flexible membrane, for example due to the pressureof the measurement gas in the control chamber, during the filling anddelivery steps are chosen to yield a desired liquid flow rate for agiven pump stroke cycle. For applications where the pumping system isbeing utilized to pump a liquid to the body of a patient, the fill anddelivery pressures are preferably chosen to be compatible withacceptable pressures for infusion of liquid to a patient. Typically, fordelivery of liquids to the vasculature of a patient, the maximummeasurement gas pressure in the pumping system will not exceed about 8psig and the minimum measurement gas pressure in the pumping system willnot exceed about −8 psig.

When liquid delivery involves performing a multiple number of pumpstroke cycles, as described above, over a period of time, in addition todetermining a liquid flow rate for a given stroke, preferred pumpingsystems will include a processor that also is configured to determine anaverage pump flow rate over the entire period of operation. An averagepump flow rate or average liquid flow rate is defined as the volume ofliquid dispensed by the pump during multiple pump stroke cycles dividedby the total time elapsed during the cycles. For applications involvingmultiple pump stroke cycles, in addition to controlling liquid flow ratevia selection and control of the force applied to the pump chambermembrane, the system can also control the average liquid flow rate byselectively varying the length of a dwell period that can be insertedbetween individual pump stroke cycles prior to filling and/or deliveringliquids from the pump chamber. The pumping systems according to theinvention can also be configured to deliver a desired total liquidvolume during operation, as well as to deliver a desired liquid flowrate as described above.

The predetermined limit to which the differences in measured volumes, ormeasured parameters related to volumes, of the pump chamber are comparedfor determining when the amount of gas in the pump chamber has exceededan acceptable value can be determined in a variety of ways. Thepredetermined value may be chosen, for example, to be reflect thedifference in volumes determined for an amount of gas present in thepump chamber that is equal to or somewhat less than the volume of thedead space in the pump chamber created by spacers, discussed above,therein. For applications where preventing air from being pumped fromthe pump chamber is critical, for example, when pumping liquid to thebody of a patient, the predetermined threshold limit may be chosen to beless than that discussed above for safety reasons. In some embodiments,a predetermined limit can be determined by injecting a maximumpermissible quantity of gas into the pump chamber, the remainder ofwhich is filled with a liquid, and determining with the pumping systemthe difference in measured volume of the pump chamber at a firstcondition of applied force/pressures to the flexible membrane and asecond condition of applied force/pressures to the flexible membrane, asdescribed in detail in the above embodiments.

As discussed above in the context of FIGS. 8 and 9, a preferred pumpdrive system according to the invention includes a variable size orificevalve which can be controlled by the processor of the system in order tomore precisely control the pressure of measurement gas applied to thecontrol chamber during filling and dispensing of liquid from the pumpchamber.

As discussed above, for such embodiments preferred systems will alsoinclude an end of stroke detection procedure to determine when liquidhas stopped flowing into the pump chamber and when liquid has stoppedflowing out of the pump chamber during filling and delivery strokesrespectively. This end of stroke detection methodology is described indetail in commonly owned copending application Ser. No. 09/108,528,which is hereby incorporated by reference in its entirety. Briefly, inpreferred embodiments, pump drive system 502 of FIG. 8 continuouslymonitors and controls the pressure of measurement gas in control chamber110 during filling and dispensing of liquid from pump chamber 108. Thesystem can detect the end of stroke as follows. During the filling ordelivery step, processor 506 controls variable size orifice valve 536 sothat the pressure of measurement gas in control chamber 110 has anaverage value essentially equal to the desired delivery or fill pressureand, in addition, includes a cyclically varying, low-amplitude variationin the pressure that is superimposed thereupon. For example, for a fillor delivery pressure in the range of a few psig, the variable componentsuperimposed can have an amplitude that differs from the average targetpressure by, for example, +/−about 0.05 psig, varying at a frequency of,for example, about 1 Hz. While the pump chamber 108 is filling oremptying, flexible membrane 112 will be in motion, and the system willdetect the cyclical variations in pressure discussed above. However, atthe end of a stroke, when the membrane is essentially no longer free tomove in at least one direction and when liquid flow into or out of thepump chamber has essentially stopped, the pressure in control chamber110 will no longer be able to be cyclically varied as described above.The system can detect this condition by continuously monitoring thepressure signal, for example, from transducer 122 on control chamber110, differentiating the pressure signal with respect to time, taking anabsolute value of the differentiated signal, and comparing the absolutevalue of the differentiated pressure signal to a minimum thresholdvalue. At the end of the stroke, when the pressure in control chamber110 is no longer cyclically varying, a derivative of the pressure withrespect to time will approach zero and, therefore, by comparing the timederivative to a minimum threshold value, the system can determine whenflexible membrane 112 has reached the end of its stroke, and can thendiscontinue filling or dispensing. In preferred embodiments, beforecomparing to the threshold value, the absolute value of the derivativeof the pressure signal with respect to time is first subjected to a lowpass filter in order to smooth the signal and derive a more stable valuetherefore.

Preferred pumping systems according to the invention are also able todetect a line blockage or occlusion in the inlet or outlet line of pumpchamber 108 during operation, and are able to create an alarm conditionand, in some embodiments, shut down the pumping cycle, when suchblockage or occlusion is detected. Such a no-flow condition is detectedby the system by comparing the volume of liquid delivered during thepump delivery stroke and the volume of liquid filling the pump chamberduring the pump chamber filling stroke and comparing the volume,determined as described above, to the known minimum and maximum volumesfor the pump chamber respectively. The system can then determine if thevolume of liquid delivered by the pump chamber or the volume of liquidentering the pump chamber differs significantly from the volumesexpected for a full stroke. If so, the system can create an alarmcondition indicating a no/low flow condition or occlusion in the lineexists. The no/low flow condition threshold value can be set based onthe needs of the various applications of the inventive pumping systemsand can be, in some embodiments, about one half of the maximum strokevolume of the pump chamber.

Certain embodiments provide an alternative way of operating a pumpchamber for delivering a liquid therefrom, which is useful forgenerally, and especially useful when delivering very small quantitiesof liquid, liquid at very low average flow rates, and where precisemeasurement is needed. The basic steps of an example embodiment of thismethod include filling the pump chamber with a liquid, isolating thepump chamber, applying a force to the flexible membrane or moveablesurface of the pump chamber, and regulating the flow of liquid from thepump chamber while maintaining the force on the membrane or surface. Forexample, in the context of pumping system 500 shown in FIG. 8, themethod may involve first filling pump chamber 108 with a liquid asdescribed previously with respect to FIG. 9, closing inlet valve 116 andtaking an initial volume measurement of the pump chamber, placingcontrol chamber 110 in fluid communication with the positive pressuretank 508 and controlling the pressure in control chamber 110 at adesired value utilizing variable size orifice valve 536, and thenselectively actuating outlet valve 120 on the outlet line 118 of thepump chamber 108 to open and close the valve for predetermined timeperiods at predetermined intervals while maintaining the desireddelivery pressure in control chamber 110. Volume measurements of pumpchamber 108 can be performed either after each pulse (opening andsubsequent closing) of outlet valve 120, or, alternatively, can beperformed after a series of pulses of the outlet valve over a measuredcumulative time interval. In this fashion, the volume delivered perpulse or the average liquid flow rate over a series of pulses can bedetermined, and the system can be configured to adjust the length of thetime periods during which outlet valve 120 is opened and to adjust thetime intervals between the pulsed openings of outlet valve 120 in orderto achieve a desired predetermined average liquid flow rate. While thepulsed delivery mode of delivering a liquid from a pump chamber has beendescribed in the context of FIG. 8, any of the other systems previouslydescribed (and other systems, as well) can also be used to perform apulsed delivery of liquid from a pump chamber.

For certain embodiments of pumping systems, it is preferred that thesystems be comprised of two separable components, one component beingreusable and including the pump drive system, and the other componentbeing removable from the reusable component. Such systems may beparticularly useful for medical applications for pumping fluids toand/or from the body of a patient. In many embodiments, the reusablecomponent may be disposable and designed for a single use.

The removable/disposable portion of the system may include the pumpchamber and the pump chamber inlet and outlet lines, including thevalves therein, and the other components which are in contact with theliquid being pumped with the pumping system. The removable/disposablecomponent of such a system is referred to herein as the “pumpingcartridge,” which pumping cartridge can be configured and designed witha plurality of pump chambers, flow paths, valves, etc., specificallydesigned for a particular application. An exemplary pumping cartridgefor use in one particular medical application is described in moredetail below.

For example, considering the example pumping systems previouslydiscussed, pumping system 100 shown in FIG. 1 may comprise a reusablepumping system component 230 coupled to a disposable pumping cartridge231, including the disposable pump chamber 108, inlet line 114, inletvalve 116, outlet line 118, and outlet valve 120. For pumping system 300shown previously in FIG. 5, the reusable component may comprise reusablesystem 302, which would be coupled in operative association with apumping cartridge 305, when the pumping system is in operation.Similarly, pumping system 400 of FIG. 7 would comprise a reusablecomponent 402 coupled to pumping cartridge 403, and pumping system 500shown in FIG. 8 would include reusable component 502 coupled to apumping cartridge 503.

For embodiments involving removable/disposable pumping cartridges andreusable pump drive systems, the pumping cartridge and the reusablecomponent are constructed and arranged to be couplable to each other.“Constructed and arranged to be couplable” as used herein indicates thatthe separable components are shaped and sized to be attachable to and/ormateable with each other so that the two components can be joinedtogether in an operative association. Those of ordinary skill in the artwould understand and envision a variety of ways to construct and arrangepumping cartridges and components of reusable systems to be couplable inoperative association. A variety of such systems which may be employedin the present invention have been described previously in commonlyowned U.S. Pat. Nos. 4,808,161, 4,976,162, 5,088,515, and 5,178,182.

Typically, the pumping cartridge and reusable component will be coupledtogether with an interface therebetween, where the reusable componentadjacent to the interface will have a series of depressions formed in asurface of the interface, which depressions are sized and positioned tomate with similar depressions in the pumping cartridge, when the pumpingcartridge and the reusable component are coupled together, so that uponcoupling, the depressions in the pumping cartridge and the reusablecomponents together form the various chambers utilized by the pumpingsystem. Also, when coupled together, the pumping cartridge and thereusable component preferably interact at an interface therebetween suchthat the interface creates a fluid impermeable/fluid-tight seal betweenthe components, so that the measurement fluid contained by the reusablecomponent and the liquid present in the pumping cartridge are not influid communication with each other during operation of the system.Those of ordinary skill in the art would readily envision a variety ofmeans and mechanisms for coupling together the pumping cartridges andreusable components to achieve the above requirements. For example, thecomponents may be held together in operative association by clips,bolts, screws, clamps, other fasteners, etc., or the reusable componentmay include slots, channels, doors, or other components as part of ahousing for holding the pumping cartridge in operative association withthe reusable component. Such techniques for coupling togetherdisposable/reusable pumping cartridges and reusable pump drive systemsare well known in the art, and any such systems are potentially usefulin the context of the present invention.

FIG. 10 shows a preferred embodiment of the interface between pumpingcartridge 503 and reusable pump drive system 502 of pumping system 500shown previously in FIG. 8. FIG. 10 is a cut-a-way view showing only theportion of reusable component 502 which mates with and is in contactwith pumping cartridge 503 when the components are coupled together inoperative association. Such portion of the reusable component willhereinafter be referred to as the “pump housing component.” Also shownin FIG. 10 is a preferred arrangement for providing valves in fluidcommunication with the liquid flow paths of the pumping cartridge, whichvalves are described in more detail below.

Pump housing component 700 includes a door 702 and a mating block 704the surface of which forms an interface when pumping cartridge 503 iscoupled to pump housing component 700. Mating block 704 has a generallyplanar surface in contact with the pumping cartridge having a variety ofdepressions 706, 708, 710 therein which mate with complementarydepressions contained within pumping cartridge 503 for forming variouschambers of the pumping system when the components are coupled together.For example, depression 706 in mating block 704 is coupled to depression712 in pumping cartridge 503 thus forming a pump chamber 108 in pumpingcartridge 503 and an adjacent control chamber 110 in mating block 704,when the components are coupled together.

As will be described in more detail below, pumping cartridge 503comprises a substantially rigid component 714 covered, on at least oneside thereof, by a flexible membrane, which in preferred embodiments isan elastic membrane. In a preferred embodiment shown, mating block 704is also covered by a flexible membrane 716 which is in contact withflexible membrane 112 covering pumping cartridge 503, when thecomponents are coupled together. Flexible membrane 716 is an optionalcomponent which provides an additional layer of safeguarding againstpotential leakage of fluids between pumping cartridge 503 and thereusable component thus preventing contamination of the reusablecomponent by the liquids in the pumping cartridge.

Upon coupling, a fluid-tight seal should be made between the flexiblemembranes and the surfaces of mating block 704 and pumping cartridgerigid component 714 forming the various chambers. In order to obtainsuch a seal, there should be some degree of compression between pumpingcartridge 503 and mating block 704 when the components are coupledtogether. In addition, seals 718 may be provided around the periphery ofthe depression within mating block 704, which seals are positionedadjacent to the periphery of complementary depressions in pumpingcartridge 503 in order to create additional compression of the flexiblemembranes for forming a leak-tight seal. Alternatively, such seals couldbe provided around the perimeter of the depressions in pumping cartridge503 in addition to, or instead of, mating block 704. Such seals may beprovided by a variety of materials, as apparent to those of ordinaryskill in the art, for example, properly sized rubber or elastomerO-rings can be used which fit into complementary grooves within matingblock 704 or, alternatively, are affixed to the mating block byadhesives, etc.

As discussed above, pumping cartridge 503, in the embodiment shown,includes a substantially rigid component 714 that is preferablyconstructed of a substantially rigid medical grade material, such asrigid plastic or metal. In preferred embodiments, substantially rigidcomponent 714 is constructed from a biocompatible medical gradepolyacrylate plastic. As will be described in more detail below,substantially rigid component 714 is molded into a generally planarshape having a variety of depressions and grooves or channels thereinforming, when coupled to the reusable component, the various chambersand flow paths provided by the pumping cartridge.

In some embodiments, the substantially rigid component of the pumpingcartridge can include a first side, which mates with the mating block,which first side contains various depressions and channels therein forforming flow paths and chambers within the pumping cartridge uponcoupling to the reusable component. This first side of such pumpingcartridges is covered with a flexible, an preferably elastic membrane,which can be bonded to the first side of the substantially rigidcomponent at the periphery thereof and/or at other locations on thefirst side. Alternatively, instead of being a single continuous sheet,the flexible membrane may comprise a plurality of individual membraneswhich are bonded to the substantially rigid component only in regionscomprising chambers, or other components, in operative association withthe reusable component.

FIG. 10 shows such an embodiment of a pumping cartridge 503 which has afirst side 720, facing mating block 704, and a second side 722, facingdoor 702 of pump housing component 700, each of which sides is coveredby a flexible membrane. First side 720 of pumping cartridge 503, asshown, includes depressions 712, 724, and 726 and is covered by flexiblemembrane 112. The second side 722 of pump cartridge 503 includes avariety of channels 728, 730 formed therein, which channels are coveredby flexible membrane 732, which is disposed on the second side 722 ofpump cartridge 503, the combination of which channels and flexiblemembrane provide fluid-tight liquid flow paths within pumping cartridge503, upon coupling to the reusable component.

The flexible membranes for use in pumping cartridge 503 and, in someembodiments, mating block 704, can be comprised of a variety of flexiblematerials known in the art, such as flexible plastics, rubber, etc.Preferably, the material comprising the flexible membranes used for thepumping cartridge is an elastic material that is biocompatible anddesigned for medical use, when used for applications where the pumpingcartridge is used for pumping liquid to and from the body of a patient.The material comprising the flexible membranes should also be selectedbased on its ability to form a fluid-tight seal with the substantiallyrigid component 714 of pumping cartridge 503 and with mating block 704of the reusable component. In a preferred embodiment, where rigidcomponent 714 of pumping cartridge 503 is formed of a clear acrylicplastic, elastic membrane 112 is comprised of polyvinyl chloridesheeting, which is about 0.014 in thick and which is hermetically sealedto the first side 720 of rigid component 714 of pumping cartridge 503.Since the elasticity of membrane 712 disposed on the second side 722 ofpumping cartridge 503 does not substantially contribute to itsperformance, it is not necessarily preferred to use an elastic materialfor membrane 712. However, for convenience and ease of fabrication,membrane 712 can be comprised of the same material as membrane 112, andcan be hermetically sealed the second side 722 of rigid component 714 ofpumping cartridge 503 in a similar fashion as membrane 112.

In the embodiment illustrated, door 702 is hinged to the body of thereusable component and can be opened or closed by an operator of thesystem, either manually, or in some embodiments, under computer controlof the processor controlling the system, so that pumping cartridge 503can be properly inserted and mated with mating block 704. Preferably,pumping cartridge 503, mating block 704, and door 702 are shaped andconfigured so that pumping cartridge 503 can only mate with the reusablecomponent in the proper orientation for operative association. Inpreferred embodiments, door 702 latches to the reusable component whenclosed. In some embodiments, the pumping system may include detectorsand circuitry for determining the position of the door and is configuredto allow operation of the system only when pumping cartridge 503 hasbeen properly installed and door 702 has been properly closed. Also, inpreferred embodiments, the pumping system is configured to prevent thedoor from being opened during operation of the system, so that thefluid-tight seal that is formed between pumping cartridge 503 and thereusable system is not compromised while the system is in operation.Door 702 also, in preferred embodiments, includes an inflatable pistonbladder 734 having an inlet line 736 which is in fluid communicationwith a fluid supply of the pumping system when the system is inoperation. Also, in preferred embodiments, adjacent to piston bladder734 and pumping cartridge 503 is an essentially planar piston surface738. After inserting pumping cartridge 503 and closing door 702, butbefore operating pumping cartridge 503, the system supplies pressurizedfluid to piston bladder 734 to create a compressive force againstpumping cartridge 503 so as to create fluid-tight seals within thesystem, as described previously.

As discussed above, pumping cartridge 503 and reusable component 502, asshown in FIG. 10, together provide a unique means of operating thevalves within pumping cartridge 503. Inlet valve 116 and outlet valve120 include valving chambers 740 and 742 which are formed from thecombination of depressions 724 and 726 within rigid component 714 andflexible membrane 112. Each valving chamber includes at least oneoccludable port 744, 746 and at least one other port 748, 750. In theembodiment shown, ports 748, 750 are not occludable by flexible membrane112. In other embodiments, ports 748 and 750 may be occludable andsimilar in construction to occludable ports 744 and 746. As shown, ports744 and 750 comprise holes within rigid component 714 of pumpingcartridge 503 allowing fluid communication between liquid flow paths 114and 118 present on the second side 722 of pumping cartridge 503 andvalving chambers 740 and 742 located on the first side 720 of pumpingcartridge 503. Occludable ports 744 and 746 also provide fluidcommunication between the valving chambers and liquid flow paths withinthe pumping cartridge. Occludable ports 744 and 746 are constructed sothat holes through which a liquid flows are located on members 749 thatprotrude from the base of the depression forming the valving chambers.In preferred embodiments, protruding members 749 have a truncatedconical shape, wherein ports 744 and 746 comprise holes in the truncatedapex of the conical protruding members.

Mated to valving chambers 740 and 742, when the pumping cartridge is inoperative association with the reusable component, are valve actuatingchambers 752 and 754 formed from depressions 708 and 710 within matingblock 704. In order to close the valves to restrict or block flowtherethrough, pumping system 500 includes valve actuators (provided inthis embodiment by the valve actuating chambers as shown) configured toselectively and controllably apply a force to flexible membrane 112tending to force the flexible membrane against an adjacent occludableport, thus occluding the port. Inlet valve 116 is shown in such a closedconfiguration. To open a valve, the pumping system can release thepositive force applied to flexible membrane 112 and, in someembodiments, can apply a negative force to flexible membrane 112 tendingto move the membrane into the valve actuating chamber. Outlet valve 120is shown in FIG. 10 in such an open configuration. Pumping system 500 isconfigured as shown to open and close the valves within pumpingcartridge 503 by selectively applying a measurement gas to the valveactuating chambers at a pressure sufficient to occlude the occludableports contained within the valving chambers. Such pressure will exceedthe pressure of any liquid contained in the valving chamber.

Gas inlet lines 756 and 758 supplying valve actuating chambers 752 and754 are connected so that they are able to be placed in fluidcommunication with a pressurized measurement gas supply source(s)contained in pumping system 500. It should be understood that in otherembodiments not shown, pumping system 500 may include valve actuatorsusing alternative means as a force applicator for applying a force toflexible membrane 112 in order to occlude occludable ports 744 and 746.In alternative embodiments, the system may include a valve actuator thatincludes a force applicator comprising, for example, a mechanicallyactuated piston, rod, surface, etc., or some other force applicatorusing an electrical or magnetic component, disposed adjacent to theflexible membrane. In preferred embodiments, as shown, the systemcomprises a valve actuator comprising a valve actuating chamber, wherethe force applicator for applying a force to the flexible membranecomprises a pressurized gas or other fluid.

As with other particular features described above, this valve andmechanism for operating the valve is particularly advantageous. Use ofsuch valves are not, however, required in all embodiments of the presentinvention and, in the context of a system design, any other valve andvalve actuator may be used.

Also shown in FIG. 10 is a preferred mechanism for providing a pressuremeasuring component for determining the pressure in control chamber 110,which may be used in some (but not all) embodiments of the presentinvention. Pumping system 500 as shown in FIG. 10 is configured so thatpressure transducers are resident on a circuit board contained withinprocessor 506 (not shown in FIG. 10), which transducers are connected influid communication with various chambers and components in the systemvia tubing or channels. For example, pressure transducer 122 (not shown)for measuring the pressure in control chamber 110 is connected in fluidcommunication with control chamber 110 via line 760 and port 762 influid communication with control chamber 110.

Preferably, after mating pumping cartridge 503 to the reusable componentand before commencement of operation, pumping system 500 is configuredto perform a variety of integrity tests on pumping cartridge 503 toassure the proper operation of the pumping system. In such embodiments,pumping system 500 includes an inlet and outlet tube occluder (notshown) for blocking the flow of fluid to and from pumping cartridge 503and for isolating the chambers and flow paths of pumping cartridge 503.After coupling pumping cartridge 503 to the reusable component butbefore priming pumping cartridge 503 with liquid, a dry pumpingcartridge integrity test can be performed. The test involves opening theinlet and outlet line occluding means so that pumping cartridge 503 isnot isolated from the surroundings and supplying all of the controlchambers and valve actuating chambers in the system with a measurementgas at a predetermined positive or negative pressure. The system thencontinuously monitors the measurement gas pressure within the variouschambers of the reusable component over a predetermined period of time.If the change in pressure exceeds a maximum allowable predeterminedlimit, the system will indicate a fault condition and terminateoperation. This dry pumping cartridge integrity test is useful fordetecting holes or other leaks within flexible membrane 112. The drypumping cartridge integrity test integrity test briefly described aboveis discussed in more detail in commonly owned copending application Ser.No. 09/193,337 incorporated by reference herein in its entirety.

After performing the dry pumping cartridge integrity test above, butbefore operation, a wet pumping cartridge integrity test can also beperformed. The test involves first priming all of the chambers and flowpaths of pumping cartridge 503 with liquid and then performing thefollowing two tests. First, the integrity of the valves within thepumping cartridge is tested by applying positive pressure to valveactuating chambers 752 and 754 to close valves 116 and 120 within thepumping cartridge, and then applying the maximum system measurement gaspressure to the control chamber 110 coupled to the pump chamber 108. Thesystem is configured to measure the volume of the pump chamber 108within the pumping cartridge, as described previously, before theapplication of pressure, and again after the pressure has been appliedto the pump chamber for a predetermined period of time. The system thendetermines the difference between the measured volumes and creates analarm condition if the difference exceeds an acceptable predeterminedlimit. The second test involves determining the fluid tightness of thevarious fluid flow paths in chambers within pumping cartridge 503. Thistest is designed to prevent the system from operating when a cartridgehas been manufactured so that there may be leakage between flow pathsand undesirable mixing of liquids within the pumping cartridge. The testis performed in a similar fashion as that described immediately aboveexcept that the valves within pumping cartridge 503 are maintained in anopen configuration with the inlet and outlet line occlusion means beingactuated by the system to isolate the pumping cartridge from itssurroundings. As before, a maximum measurement gas pressure is appliedto the control chamber of the reusable component, and the volumecontained in the pump chamber is determined before and after applicationof pressure. Again, the system is configured to create an alarmcondition and discontinue operation if the differences in measuredvolume exceed an allowable predetermined limit. It should be understoodthat while the various integrity tests and preferred modes of operatinga pumping cartridge have been described in the context of system 500 andpumping cartridge 503 illustrated in FIG. 10, the methods and tests canalso be applied and employed for other configurations of the pumpingcartridge and reusable system.

FIGS. 11 a-11 f show various views and features of one particularembodiment of a multi-functional pumping cartridge according to theinvention which includes a plurality of pump chambers, valving chambers,and fluid flow paths therein. The pumping cartridge shown in FIGS. 11a-11 f is similar in construction to pumping cartridge 503 shown in FIG.10, in that the pumping cartridge includes a substantially rigidcomponent with various depressions and channels/grooves therein coveredon each side with a flexible membrane that is hermetically sealedthereto. FIG. 11 a is an en face view of the first side of pumpingcartridge 800, which first side is coupled to and in contact with aninterface of a mating block on a complementary reusable system when thepumping cartridge is in operation. As discussed below, except for theparticular arrangement and number of components, pumping cartridge 800is similar in overall design to that described previously in the contextpumping cartridge 503 of FIG. 10.

Pumping cartridge 800 includes a plurality of inlet and outlet lines802, 804, 806, 808, 810, 812, 814, 816, 818, and 820 for connecting thevarious flow paths of the pumping cartridge in fluid communication withlines external to the pumping cartridge. In one preferred embodiment,pumping cartridge 800 is utilized for pumping blood from the body of apatient, treating the blood, or components thereof, and returningtreated blood and other fluids to the body of the patient. For suchembodiments, pumping cartridge 800 is preferably disposable and designedfor a single use, and is also preferably biocompatible and sterilizableso that it may be provided to the user as part of a sterile, single-usepackage.

As shown in FIG. 11 a, pumping cartridge 800 includes two large pumpchambers 822 and 824 and a third smaller pump chamber 826. Pumpingcartridge 800 also includes a plurality of valving chambers 827, 828,829, 830, 832, 834, 836, 838, 840, 842, 846, 848, 850, 852, 854, 856,and 858 for controlling and directing the flow of liquid through thevarious liquid flow paths and pump chambers provided within pumpingcartridge 800. The construction of each of the pump chambers and valvingchambers above is similar to that shown previously for pumping cartridge503 shown in FIG. 10. Pumping cartridge 800 also includes the novelinclusion of a bypass valve provided by a bypass valving chamber 860 andan integrated filter element 862, the function and structure of whichcomponents are explained in more detail below.

In operation, pumping cartridge 800 is coupled in operative associationwith a complimentary mating block of a reusable component havingdepressions and pneumatic (in appropriate embodiments) connectionstherein for actuating the various pump chambers and valving chambers ofthe pumping cartridge in a similar fashion as that previously described.The reusable component also preferably includes an occluder 864 includedtherein, disposed adjacent to tubing in fluid communication with thevarious inlet/outlet ports of the pumping cartridge, for occluding thevarious inlet and outlet lines in fluid communication with the pumpingcartridge when performing various integrity tests as describedpreviously and/or for other purposes where it is desirable tofluidically isolate the pumping cartridge. In preferred embodiments, theoccluder is constructed as described below and is configured to occludethe tubing unless a force is applied to the occluder, for example bysupplying a pressurized fluid to a bladder tending to move the occluderto unocclude the various tubing. In such embodiments, in a fail safecondition (e.g. during a power failure) the occluder will be configuredto occlude the tubing, thus preventing undesirable liquid flow to and/orfrom a source or destination (especially when such source or destinationis the body of a patient.

As described below, the reusable system that is constructed and arrangedfor operative association with pumping cartridge 800 will also includevarious processors (or a single processor configured to perform multiplefunctions, or other suitable hardware or software mechanisms) toselectively control and operate the various components of pumpingcartridge 800 for performing various user designated pumpingapplications. It will be understood by those of ordinary skill in theart that pumping cartridge 800 can be used for an extremely wide varietyof potential pumping and fluid metering applications depending on themanner in which the various components contained therein are operatedand controlled. Each of such uses and applications are deemed to bewithin the scope of the present invention.

The flow paths within pumping cartridge 800 which are comprised ofchannels formed on the first side of the pumping cartridge (the sidefacing the viewer), for example flow path 866, are shown as solid lines.Flow paths that are formed from channels disposed on the second(opposite) side of pumping cartridge 800, for example flow path 872, areshown in FIG. 11 a by dashed lines. As can be seen in FIG. 11 a, in theembodiment shown, filter element 862 is also disposed on the second sideof pumping cartridge 800. As will be described in more detail below, apreferred function of filter element 862 is to filter fluids beingpumped from pumping cartridge 800 to the body of a patient to remove anyblood clots or aggregated material therefrom.

The structure of pumping cartridge 800 can be seen more clearly from thecross-sectional view of FIG. 11 b. Pumping cartridge 800 includes asubstantially rigid component 876 having a series of depressions andchannels therein forming the various chambers and flow paths of thepumping cartridge. Pumping cartridge 800 has a first side 890, which isdisposed against a mating block of the reusable component in operation,and a second side 892, which is disposed against the door of the pumphousing component when in operation. First side 890 is covered byflexible membrane 112 hermetically sealed around the periphery of rigidcomponent 876. Second side 892 is similarly covered by flexible membrane732. Clearly visible are liquid flow paths 866 and 874, both of whichare disposed on first side 890 of pumping cartridge 800 and liquid flowpaths 864 and 872 disposed on second side 892 of pumping cartridge 800.Pump chambers 822 and 824 are formed from curved depressions 894 and 896in first side 890 of rigid component 876. Clearly visible are spacers868 which comprise elongated protuberances having bases 898 attachedwithin the pump chambers to rigid component 876 and ends 900 extendinginto pump chambers 822 and 824 toward flexible membrane 112. Aspreviously described, these spacers prevent contact of flexible membrane112 with the base of depressions 894 and 896 in rigid component 876during pumping and provide a dead space which inhibits pumping of gasfrom the pump chambers during operation. In this embodiment, the spacersare small, evenly spaced bumps located on a wall of the pump chamber.The size, shape and positions of the spacers can be changed and stillserve the purpose of reducing risk of passing gas through the pumpchamber.

Referring to FIG. 11 b, filter element 862 includes a filter 882disposed on second side 892 of rigid component 876. Filter 882 ispreferably substantially planar and is disposed adjacent to second side892, spaced apart therefrom by spacers 870, so that the filter and theregion of second side 892 to which it is attached are essentiallycoplanar. During operation of the pumping cartridge for pumping liquidto a patient, fluid to be pumped to the patient is directed along flowpath 874 to the inlet port 904 of filter element 862 (see FIG. 11 a)into space 906 separating filter 882 from second side 892, throughfilter 882, and out of filter element 862 through occludable port 980(see FIG. 11 a). In order to prevent fluid from bypassing filter 882within filter element 862, filter element 862 should be sealed to secondside 892 of rigid component 876 along its periphery in a fluid-tightfashion. Also, for embodiments where filter element 862 is functioningas a blood clot filter, filter 882 preferably has pores therein whichare larger in diameter than the diameter of a typical human blood cell,but which are small enough to remove a substantial fraction of clottedblood or aggregated blood cells that may be present in a liquid pumpedtherethrough. In preferred embodiments, filter 882 comprises a polyesterscreen, in one embodiment having pore sizes of about 200 μm with about a43% open area.

FIG. 11 c is a cross-sectional view of outlet valving chamber 830.Outlet valve 830 has a structure which is representative of the valvingchambers provided in pumping cartridge 800. The structure of valvingchamber 830 is substantially similar to the structure of the valvingchambers in pumping cartridge 503 shown in FIG. 10 previously. Valvingchamber 830 is formed in first side 890 of rigid component 876 ofpumping cartridge 800 and includes one occludable port 920 in fluidcommunication with liquid flow path 922 on second side 892 of thepumping cartridge and a non-occludable port 924 in fluid communicationwith outlet line 926.

FIG. 11 d shows an essentially equivalent valving chamber for analternative embodiment of a pumping cartridge having an essentiallyrigid component 932 covered on only a single side by a flexiblemembrane. Analogous components of the alternative valve embodiment ofFIG. 11 d are given the same figure labels as in FIG. 11 c forcomparison.

Referring again to FIG. 11 a, the function of bypass valving chamber 860and filter element 862, as well as the flexibility of operation ofpumping cartridge 800, will be explained in the context of a particularembodiment involving an application utilizing pumping cartridge 800 thatincludes removing blood from the body of a patient, pumping the blood tovarious selectable destinations with pumping cartridge 800, andreturning treated blood or other fluids to the body of a patient. Aswill be described in detail below, it is desirable, in such anembodiment, to pump fluids which are being returned to the body of apatient through filter element 862 to remove any clots or aggregatestherefrom, and to bypass filter element 862 when withdrawing blood froma patient with pumping cartridge 800. When in operation, pumpingcartridge 800 is preferably coupled to a reusable component such thatpumping cartridge 800 is oriented essentially vertically with thevarious inlet and outlet lines pointing up. As illustrated, inlet/outletport 816 is in fluid communication with a syringe or shunt 950 insertedinto the vasculature of a patient. Blood withdrawn from the patient andfluid returned to the patient flows through inlet/outlet 816 and alongliquid flow path 872 within pumping cartridge 800. Liquid flow path 872is in fluid communication with bypass valving chamber 860 via a firstport 952. Also in the illustrated embodiment, inlet valve 832 of smallpump chamber 826 is in fluid communication with a supply ofanticoagulant 980, and outlet valve 830 of pump chamber 826 is in fluidcommunication with the syringe/shunt 950 inserted into the body of apatient. In this configuration, small pump chamber 826 can be utilizedas an anticoagulant delivery pump for pumping an anticoagulant to aninjection site of a patient in order to keep the injection site fromblocking and in order to provide anticoagulant to blood removed from thepatient.

As explained in greater detail below, the function of bypass valvingchamber 860 is to selectively permit liquid flow along a first liquidflow path bypassing filter element 862, or alternatively, to block flowalong the first fluid flow path and direct flow along a second liquidflow path, which second liquid flow path directs the liquid so that itflows through filter element 862. Also, as discussed below, valvingchamber 860 also permits liquid flow along both liquid flow paths aboveto be simultaneously blocked if desired. For the present embodimentwhere blood is being removed from a patient and, subsequently, liquidsare being returned to a patient, the first liquid flow path describedabove will be selected by the system, by utilizing bypass valvingchamber 860, when removing blood from the patient, and the second liquidflow path described above will be selected by the system, utilizingbypass valving chamber 860, when liquids are being pumped from thepumping cartridge to the patient.

Bypass valving chamber 860 is comprised of two adjacent subchambers 970,972 separated by a partition 974 therebetween, which has an aperturetherethrough permitting unrestricted fluid communications between thetwo subchambers. “Subchamber(s)” as used herein refers to regions of achamber within a pumping cartridge, which region includes an internalpartition, that are adjacent and are separated one from the other by theinternal partition, where the internal partition allows unrestrictedfluid communication between the regions.

The structure of bypass valving chamber 860 is shown in greater detailin the cross-sectional view of FIG. 11 e. Referring to FIG. 11 e,partition 974 separates the bypass valving chamber into subchambers 970and 972 and is in fluid-tight contact with flexible membrane 112 whenthe pumping cartridge is coupled to a reusable component. When coupledwith a reusable component, subchamber 970 and subchamber 972 can each becoupled adjacent to and in operative association with a separate andindependently controllable valve actuating chamber in the reusablecomponent, which is each disposed adjacent to the subchamber. The valveactuating chambers can be independently operated to selectively occludeand open occludable port 980 in subchamber 970 and occludable port 982in subchamber 972.

Also shown in FIG. 11 e, for the purposes of illustrating the functionof bypassing valving chamber 860, is a schematic representation of asecond liquid flow path through the bypass valving chamber where theliquid is forced through filter element 862. Referring to both FIGS. 11a and 11 e together, consider a first step in a pumping method using thepumping cartridge during which blood is withdrawn from the patient byfilling pump chamber 822 and/or 824. During this step, as discussedabove, it is desirable to flow blood from the patient through bypassvalving chamber 860 along a first liquid flow path which bypasses filterelement 862. This can be accomplished by occluding occludable port 980in subchamber 970 while leaving occludable port 982 in subchamber 972non-occluded. In such a situation, blood will flow from the patient,along liquid flow path 872 into subchamber 970 through port 952, fromsubchamber 970 to subchamber 972 through opening 990 in partition 974,and will exit subchamber 972 through occludable port 982. For asituation where treated blood or another liquid such as plasma or salineis being pumped with pump chamber 822 and/or 824 through line 959 tobypass valving chamber 860 to be reinfused into a patient, as discussedabove, it is desirable to operate the bypass valving chamber so that theliquid flows along the second liquid flow path, which passes the liquidthrough filter element 862 prior to returning it to the patient. In sucha situation, the second liquid flow path can be selected by occludingoccludable port 982 in subchamber 972 and leaving non-occludedoccludable port 980 in subchamber 970. In which case fluid will flowalong liquid flow path 959 and subsequently along liquid flow path 874to the inlet port 904 of filter element 862. Liquid will not be able toenter subchamber 972 due to the occlusion of occludable port 982. Theliquid, after entering filter element 862, will pass through filter 882and exit filter element 862 by entering subchamber 970 throughoccludable port 980. The liquid will then exit subchamber 970 throughport 952 and flow along liquid path 872 for return to the patient.

FIG. 11 f shows an essentially equivalent bypass valving chamber 861 foran alternative embodiment of a pumping cartridge having an essentiallyrigid component 932 covered on only a single side by a flexiblemembrane. Analogous components of the alternative bypass valveembodiment of FIG. 11 f are given the same figure labels as in FIG. 11 efor comparison.

During other operations utilizing pumping cartridge 800, it may bedesirable to operate bypass valving chamber in order to block liquidflow along both the first liquid flow path (bypassing the filterelement) and along the second liquid flow path (wherein the liquid ispassed through the filter element). Flow can be blocked along both theabove-mentioned liquid flow paths utilizing bypass valving chamber 860simply by occluding both occludable port 980 and 982 simultaneously.

It should be understood that while the operation of bypass valvingchamber has been described in the context of pumping blood and liquidsto and from a patient and for the purpose of selectively passing suchliquids through a filter or bypassing the filter, the bypass valvingchamber provided by the invention can be used for a wide variety ofother purposes, wherein it is desirable to selectively choose liquidflow along a first and second liquid flow path. It should also beunderstood that while in the above-mentioned embodiment liquids flowingalong a first and second liquid flow path through bypass valving chamber860 flow through the chamber in a particular direction, in otherembodiments, the direction of liquid flows along the first and secondliquid flow path could be reversed or could be co-directional in eitherdirection.

Referring again to FIG. 11 a, a variety of exemplary sources anddestinations in fluid communication with pumping cartridge 800 areillustrated in the exemplary embodiment shown, in addition toanticoagulant source 980 and syringe/port 950, pumping cartridge 800 isalso connected to a source of saline 1000, a plasma storage container1002, a centrifuge 1004 for separating blood cells from plasma and/orcertain blood cells from each other, and a treatment chamber 1006 forperforming a treatment on blood, plasma, or blood cells. By selectivelyoperating the various pump chambers and valving chambers within thepumping cartridge, liquids can be pumped to and from various sources anddestinations for a variety of purposes and treatments as would beapparent to those of ordinary skill in the art.

In one particular embodiment, pumping cartridge is utilized as part of asystem designed for use in photopheresis treatment to the bloodcomponents of a patient as part of a therapy for the treatment ofvarious blood disorders and treatments such as in the treatment of HIVinfection, to prevent the rejection of transplants, or for treatment ofvarious autoimmune disorders, for example scleroderma. In thisembodiment, the patient is first given a dose of the drug psoralen about30 min. prior to blood treatment. The psoralen molecules attach tospecific undesirable blood components. In this embodiment, treatmentchamber 1006 is configured to expose the fractionated blood componentsof a patient to ultraviolet A (UVA) light to activate the psoralenmolecules which in turn modify the blood components to which they arebound so that upon reinfusion into the patient, the modified bloodcomponents are either recognized by the patient's immune system andeliminated, or they are immobilized and prevented from harming thepatient (for guidance in performing the UVA treatment and configuring aUVA treatment chamber reference is made to U.S. Pat. No. 5,147,289 toEdelson, incorporated herein by reference in its entirety). Pumpingcartridge 800, for this embodiment, can be operated to initially removeblood from the patient, pump the blood to centrifuge 1004 to fractionatethe various components according to the needs of the particulartreatment protocol, direct one or more blood components to treatmentchamber 1006 for UVA activation and, if desired one or more othercomponents back to the patient or to a storage container, such as plasmareturn 1002, and finally pump the UVA-treated blood components back tothe patient, as well as, if desired or required, saline from salinecontainer 1000 and/or any blood components contained in plasma returncontainer 1002. It will be apparent to those of ordinary skill in theart that the above outlined protocol may be modified in a variety ofways and customized for specific procedures without departing from thescope of the invention.

In general, pump chambers 822, 824 and 826 of pumping cartridge 800 canbe operated utilizing a reusable component including a pump drive systemconstructed according to any of the embodiments previously described forsuch systems. Pump chambers 822, 824, and 826, when pumping a liquid tothe body of a patient, preferably are operated utilizing pump strokecycles including air detection and purging steps, as describedpreviously. FIG. 11 a illustrates that pumping cartridge 800 includesseveral additional design safeguards for preventing air, or other gas,from being pumped to the body of a patient. For example, pump chamber826, which is configured in this example to pump an anticoagulant to theinjection port of a patient for certain embodiments where the pumpingcartridge is utilized for blood pumping, has an inlet port 1008 locatedat the top of the pump chamber and an outlet port 1010 located at thebottom of the pump chamber. This configuration results in any air in thepump chamber rising toward the top of the pump chamber so that it isless likely to be pumped through the outlet port before being detectedby the system. Similarly, all liquid pumped to the patient by pumpchambers 822 and 824 are pumped along liquid flow path 959, which is influid communication with valving chambers 846 and 854 which, in turn,are in fluid communication with ports 1012 and 1014 located at thebottom of pump chamber 822 and 824, respectively. Thus, as with pumpchamber 826, any liquid pumped to the body of a patient using pumpchambers 822 or 824 must exit the pump chambers through the bottom port.Similarly, filter element 862 is constructed so that its inlet 904 islocated near the top of the filter element, and its outlet 980 islocated near the bottom. This arrangement provides an additional layerof protection in that any liquids being pumped to the patient from pumpchambers 822 or 824 are first diverted through filter element 862 bybypass valving chamber 860, and any gases contained in such liquids willtend to collect near the top of the filter element and will be inhibitedfrom being pumped to the patient. In contrast, FIG. 11 a shows that themajority of liquid flow paths in fluid communication with destinationsother than the body of a patient, for example plasma return 1002 andcentrifuge 1004, are, in turn, in fluid communication with ports 1016and 1018 located at the top of pump chambers 822 and 824, respectively.When pumping to such destinations, it is typically not critical if airis present in the pumped liquid. During operation, these destinations,for example port 808 and 812, may be used by the system as locations towhich to purge any air that is detected in pump chambers 822 and 824during pump cycles in which a liquid is being pumped to the body of apatient. Any air detected in pump chamber 826 during operation maysimilarly by purged to port 820 in fluid communication with theanticoagulant supply.

FIG. 11 a also shows that both pump chambers 822 and 824 contain similarfluidic connections to all of the sources and destinations provided by apumping cartridge 800 (except ports 818 and 820 utilized solely by pumpchamber 826). Accordingly, pump chambers 822 and 824 may be operatedindividually and independently of each other, in some embodiments, sothat liquids pumped with each chamber have a different source anddestination or, in other embodiments, pump chambers 822 and 824 may beoperated so that their inlet and outlet ports are in fluid communicationwith common sources and destinations. In the latter embodiments, thepumping system utilizing pumping cartridge 800 can be operated so thatthe fill and pump strokes of pump chambers 822 and 824 are synchronizedso that as one chamber is filling the other chamber is dispensing, andvice versa. Utilizing such an operating protocol, it is possible tooperate pump chambers 822 and 824 to achieve a nearly continuous,uninterrupted flow between a desired source and destination.

For embodiments where pump chamber 826 is utilized as an anticoagulantpump, the desired average flow rate to be delivered by the pump chambermay be quite low. In such embodiments, it may be preferable to operatepump chamber 826 utilizing the pulsed delivery protocol describedpreviously. As described previously, in such embodiments, pump chamber826 is first filled with anticoagulant, inlet valve 832 is closed, aforce is applied to flexible membrane 112 adjacent to the pump chamber,and outlet valve 830 is pulsed by selectively opening and closing theoutlet valve for predetermined periods of time at predeterminedintervals, which intervals and predetermined periods of time arecontrolled to yield a desired average liquid flow rate. Anticoagulantpump chamber 826 is typically operated to deliver anticoagulant onlywhile either pump chamber 822 or 824 is being filled with bloodwithdrawn from the body of the patient. Additionally, anticoagulant pumpchamber 826 may also be advantageously utilized to dispenseanticoagulant when pump chambers 822 and 824 are not pumping liquids toor from the body of the patient but are being utilized for otherpurposes. In such cases, it may be desirable to continuously, orintermittently dispense a small quantity of anticoagulant with pumpchamber 826 in order to assure that syringe/port 950 remains unoccluded.A pulsed delivery, as described above, may be utilized for operating theanticoagulant pump in such applications. For such applications, it isbelieved that the pulsed delivery of anticoagulant to the injection canhave beneficial effects for keeping the site from clotting anddislodging small clots when compared to a continuous delivery of anticoagulant to the site. In addition, preferred embodiments of systemsconfigured to provide pulsed delivery of anticoagulant are configured tocontinuously monitor the quantity/flow rate of anticoagulant to thepatient and can adjust the flow rate by changing and controlling thepositive pressure applied to the pump chamber during pulsed delivery aswell as by changing the pulse duration and interval between pulses. Suchcapability allows for improved flow rate delivery volume control forapplications where the anticoagulant is being delivered to a site atvariable pressure, for example an artery of a patient.

When anticoagulant pump 826 is being utilized to dispense anticoagulantwhile pump chambers 822 and/or 824 are filling with blood from thepatient, the pulse duration and interval between pulses of outlet valve830 for delivering anticoagulant from pump chamber 826 can be selected,in preferred embodiments, so that the average liquid delivery rate ofthe anticoagulant is a desired predetermined fraction of the flow rateof blood to pump chambers 822 and/or 824 while they are being filledwith blood from the patient. In other embodiments, it may be desirableto operate pump chamber 826 to provide an average liquid flow ratedelivered from the pump chamber that is a predetermined fraction of theliquid flow rate of pump chamber 822 and/or 824 during a liquid deliverystroke. In yet other embodiments, pump chamber 826 may be operated sothat the average liquid flow rate delivered from the chamber is apredetermined fraction of a liquid flow rate measured for a completepump stroke (including fill and delivery) of pump chamber 822 and/or 824or, in yet another embodiment, is a predetermined fraction of an averageliquid flow rate (calculated over several pump stroke cycles) of pumpchambers 822 and/or 824. It is also to be understood that instead ofpump chamber 826 being operated to provide a liquid flow rate that is apredetermined fraction of a liquid flow rate provided by pump chambers822 and/or 824, alternatively, pump chamber 822 could be operated toprovide a liquid flow rate which is a predetermined fraction of a liquidflow rate of pump chamber 824, or vice versa.

As discussed previously, preferred components of the pump housingcomponent of the reusable system include an occluder bar and mechanismfor actuating the bar to selectively occlude the tubing attached influid communication with a pumping cartridge. One embodiment of a pumphousing component including an occluder bar and actuating mechanism isshown in FIGS. 12 a and 12 b. Pump housing component 1100 shown in FIGS.12 a and 12 b includes a spring occluder bar 1102. In the illustratedembodiment, long arm 1104 is pivotally attached to the mating block 1105of pump housing component 1100 at pivot 1106. As discussed previously inthe context of FIG. 10, mating block 1105 will also contain depressions(not shown) forming control and valving chambers, etc. and will beconstructed and arranged to mate to the pumping cassette. Occluder bar1102 has an occluder end that is preferably at about a right angle withrespect to the rest of the occluder bar when the occluder is in anoccluding configuration as shown in FIG. 12 b. The occluder end 1108, inthe illustrated embodiment, attached to one end of a spring 1110 that isdisposed in a spring housing 1112. The spring housing, in turn, ispreferably rigidly attached to mating block 1105. Occluder end 1108 isable to move through the spring housing 1112 by compressing andexpanding the spring 1110. The occluder end 1108 terminates at anoccluder tip 1114 which is positioned adjacent to, and preferablyapproximately perpendicular to, fluid lines 1116 attached to theinlet/outlet ports of pump cassette 800.

As discussed previously, cassette 800 is held against the mating block1105 on pump housing component 1100 cassette door 1118 disposed againstthe second side of the cassette and opposite the mating block. As shownin FIG. 10 previously, cassette door 1118 preferably includes a pistonbladder (not shown) that provides additional mating force to thecassette to create a fluid-tight seal with the mating component. Thecassette door 1118 preferably extends beyond cassette 800, thus formingan occluder backstop 1120 disposed adjacent to the fluid lines 1116 andopposite occluder tip 1114. In the illustrated embodiment, an occluderbladder 1122 is disposed between long arm 1104 and mating component1105. Occluder bladder 1122 can be pressurized to unocclude tubes 1116with any hydraulic fluid, but in a preferred embodiment the hydraulicfluid comprises air. The occluder bladder 1122 can be supplied withhydraulic fluid via a supply line (not shown), which line in turn can beconnected to a pressure reservoir or a pump. The supply line alsopreferably includes a valve that can be selectively opened to deflatethe bladder and occlude tubes 1116. In a preferred embodiment, the valvewill fail open, for example if power to the system is interrupted. Whenoccluder bladder 1122 is inflated, the bladder expands against long arm1104 and displaces occluder tip 1114 away from occluder backstop 1120,thereby opening fluid lines 1116. As the occluder tip 1114 is displacedaway from occluder backstop 1120, spring 1110 is compressed to asufficient degree such that when released, the occluder tip preferablydelivers at least a 10 lb closing force on each of the fluid lines 1116.In one preferred embodiment, the maximum displacement of the occludertip 1114 upon actuation is about 0.25 inch.

In the embodiment illustrated in FIGS. 12 a and 12 b, pivot 1106 islocated at the end of long arm 1104, opposite occluder end 1108 withoccluder bladder 1122 disposed between long arm 1104 and mating block1105. In an alternative embodiment 1130 shown in FIGS. 12 c and 12 d,the pivot 1132 can be placed on the long arm 1134 at an intermediatelocation along its length, preferably close to occluder end 1136, withthe occluder bladder 1122 being disposed between long arm 1134 and anoccluder frame 1138 that is located opposite and at a spaced distancefrom mating block 1140.

Referring again to FIGS. 12 a and 12 b, the illustrated embodiment alsoincludes a hinge 1124 that is incorporated into occluder bar 1102thereby allowing the occluder end 1108 to rotate about the hinge as theoccluder bar is pivotally displaced during opening and occlusion oftubing 1116. Rotation of occluder end 1108 about hinge 1124 allows theoccluder end to maintain a more parallel orientation with respect tospring 1110 in spring housing 1112, and thereby reduces the possibilityof any spring hold-up during operation.

A preferred arrangement of an occluder mechanism is shown in FIGS. 12 eand 12 f. Occluder mechanism 1150 eliminates the coil spring and springhousing of the previously illustrated embodiments by employing a novelspring plate 1152 mounted to an occluder frame 1154 attached to reusablecomponent 1156. In the embodiment illustrated, the spring plate isconnected to occluder frame 1154 by a pair of pivot pins 1166, 1168which are, in turn, mounted on the occluder frame. Spring mounts 1158,1160 are preferably firmly attached to spring plate 1152. In alternativeembodiments, the spring plate can be attached directly to the occluderframe or attached to the occluder frame be any alternative meansapparent to those of ordinary skill in the art.

The spring plate 1152 can be constructed from any material that iselastically resistant to bending forces and which has sufficientlongitudinal stiffness (resistance to bending) to provide sufficientrestoring force, in response to a bending displacement, to occlude adesired number of collapsible tubes. In the illustrated embodiment, thespring plate is essentially flat and in the shape of a sheet or plate.In alternative embodiments, any occluding member that is elasticallyresistant to bending forces and which has sufficient longitudinalstiffness (resistance to bending) to provide sufficient restoring force,in response to a bending displacement to occlude a desired number ofcollapsible tubes may be substituted for the spring plate. Suchelongated members can have a wide variety of shapes as apparent to thoseof ordinary skill in the art, including, but not limited to cylindrical,prism-shaped, trapezoidal, square, or rectangular bars or beams,I-beams, elliptical beams, bowl-shaped surfaces, and others.

In one preferred embodiment, the spring plate 1152 is in the shape of anessentially rectangular sheet and is constructed of spring steel havinga thickness that is preferably less than 1/10 its length (the distancebetween pivot 1158 and 1160). While the particular dimensions of springplate 1152 must be determined based on factors which will vary dependingon the application, such as the modulus of elasticity of the materialfrom which it is constructed, the shape and thickness of the occludingmember the number of tubes to be occluded, the stiffness of the tubes,and other factors as apparent to those of ordinary skill in the art, ina particular preferred embodiment, the spring plate 1152 is constructedfrom spring steel with a thickness of about 0.035 in. The width (thedimension into the plane of the figures) of the spring plate 1152 isselected to enable the plate to occlude all the fluid lines going intoor out of cassette 800. The length of the spring plate 1152 can bedetermined by considering factors such as the required displacement ofoccluder blade 1164, the mechanical properties of the fluid lines, theyield point and elastic modulus of the spring plate material, and thethickness of the spring plate as mentioned above. Those of ordinaryskill in the art can readily select proper materials and dimensions forspring plate 1152 based on the requirements of a particular application.In one exemplary embodiment where the pumping cartridge includes fivefluid lines to be occluded, the spring plate is constructed from springsteel and has a thickness of 0.035 inch, a width of 4 inches, and alength of 6.1 inches.

In the illustrated embodiment, rear spring mount 1158 is pivotallyattached to the occluder frame 1154 by a rear pivot pin 1166 located ata fixed point on the occluder frame. The spring mount 1158 can, in someembodiments, be a separate piece from the spring plate 1152, which pieceis rigidly attached to the spring plate or, in other embodiments, thespring mount 1158 can be integrated into the spring plate, for example,by looping the edge of the spring plate to form a cylinder capable ofaccepting a pivot pin. The forward spring mount 1160 is attached to theoccluder frame 1154 by a forward pivot pin 1168 that can slide in adirection parallel to the length of the spring plate 1152 in a pivotslot 1170 located on the occluder frame 1154. An occluder blade 1164which moves as the spring plate 1152 is bent, is pivotally attached tothe forward pivot pin 1168.

The force required to permit occluder blade 1164 to occlude tubing 1116is provided by the longitudinal stiffness of spring plate 1152. Uponapplying a force to the surface of spring plate 1152 in a directionessentially perpendicular to the surface of the plate (as shown in FIG.12 e), the column stability of the spring plate is disrupted resultingin a buckling of the spring plate causing it to bow and decreasing thelongitudinal distance between pivot pins 1166 and 1168. This decrease indistance upon bowing of spring plate 1152 in turn creates a displacementof forward pivot pin 1168 within pivot slot 1170, which displacementcauses withdraw of occluder blade 1164 from tubing 1116 thereby openingtubing 1116 to allow fluid in/out of pumping cartridge 800. Inalternative embodiments, the force for bending need not be applieddirectly to a surface of the occluding member with a component of theforce in the direction of bending as illustrated. In some alternativeembodiments forces utilized for bending the occluding member may beapplied to a surface of the member indirectly via components attached tothe surface, force creating fields (e.g. electrostatic or magneticfields), etc., or, alternatively, force may be applied to one or moreends of the occluding member in a direction essentially perpendicular tothe bending direction in order to bend the occluding member.

In other alternative embodiments, occluder blade 1164 may not includethe pivot pin and pivot slot, but may instead be rigidly attached to thespring plate 1152. In yet other embodiments, the occluder blade may beeliminated altogether with the edge of the spring plate or otheroccluding member positioned adjacent to the tubing so that theplate/member can open and occlude the tubing as it is during bending andrelaxation respectively.

In the illustrated embodiment, occluder frame 1154 is mounted to matingblock 1172. The mating block 1172 mates to the first face of a pumpingcartridge 800. The pumping cartridge 800 is held in place by a door 1174(mating block 1172 and door 1174 can include additional components (notshown), such as piston bladders, depressions for forming chambers, etc.as discussed previously). The mating block 1172 and door 1174 can extendbeyond the pumping cartridge 800 as shown to allow the tubing 1116 to beoccluded by occluder blade 1164. The mating block 1172 incorporates aslot 1176 through which the occluder blade 1164 can be displaced. Theslot can be sized and positioned to enable occlusion of all of the fluidlines 1116 entering and exiting the pumping cartridge 800 when theoccluder blade 1164 is displaced through the slot 1176 so that itoccludes the fluid lines 1116 by pinching them against an extendedportion 1178 of the door.

In the illustrated embodiment, a force actuator for applying a bendingforce to the spring plate comprises an inflatable occluder bladder 1182.The occluder frame 1154 includes a bladder support 1180 housing aninflatable occluder bladder 1182 disposed against the spring plate 1152.The occluder bladder 1182 may be inflated with any hydraulic fluid butin a preferred embodiment air is used as the hydraulic fluid. Theinflatable occluder bladder 1182 can be supplied with air via an airline 1184 for either inflating or deflating the bladder. In a preferredembodiment, the air line 1184 can be connected to a three-way valve 1186controlled by a processor, wherein the occluder bladder 1182 can beplaced in fluid communication with either a vent line 1188 for deflatingthe occluder bladder or a pressure supply line 1190 for inflating theoccluder bladder.

FIG. 13 illustrates one embodiment for the overall architecture andconfiguration of a reusable component, including a pumping system, forcoupling to and operating a pumping cartridge 800 shown in FIG. 11 a.Reusable component 1050 includes three levels of control and includes avariety of individual systems or modules for controlling and operatingvarious components of pumping cartridge 800. Reusable system 1050includes an overall system controller and user interface 1052 whichsends commands to and receives inputs from a master pump system controlmodule 1054. The controller/interface may be implemented using amicroprocessor and associated software or using some other mechanism.Master module 1054, in turn, sends commands to and receives input fromindividual pump drive system modules 1056, 1058, 1060, as well as a doorcontrol module 1062. The master module 1054 may also include amicroprocessor and appropriate software. Reusable system 1050 alsoincludes a power supply 1064 for providing electrical power to thevarious modules, and an air pump 1066, which is utilized for providingpressurized measurement gas to the fluid supply tanks of the system. Airpump 1066 is pneumatically connected to master module 1054 which, inturn, is pneumatically connected to the individual pump modules and thedoor module.

Door module 1062 contains all necessary hardware and pneumaticconnections to provide fluid-tight coupling between pumping cartridge800 and a pump housing component of the reusable system. Door module1062 also preferably contains a piston bladder and piston, which bladderis in pneumatic communication with master module 1054 via pneumatic line1068. The configuration of door module 1062 can be similar to that shownpreviously in FIG. 10, with modifications made to accommodate the size,shape, and fluidic connections of pumping cartridge 800, as would beapparent to one of ordinary skill in the art. In addition, in preferredembodiments, door module 1062 also includes an occluder, which can besimilar to occluder 864 shown in FIG. 11 a, which is operated bysupplying pressurized measurement gas to an occluder bladder (not shown)which forces the occluder against tubing in fluid communication with thevarious inlet and outlet ports of pumping cartridge 800 to collapse andocclude the tubing, the structure and function of such tubing occludersbeing known and understood in the art. Pneumatic line 1068 from mastermodule 1054 also, in such embodiments, provides pressurized measurementgas to the occluder bladder.

Each of pump modules 1056, 1058, and 1060 are preferably similar indesign, and each is dedicated to the operation of an individual pumpchamber, and its associated valves, provided in pumping cartridge 800.For example, pump module 1 (1056) can be configured to operate pumpchamber 822, and its associated valves, pump module 2 (1058) can beconfigured to operate pump chamber 824, and its associated valves, andpump module 3 (1060) can be configured to operate pump chamber 826, andits associated valves. Each pump module is in pneumatic communicationwith door module 1062, in order to supply measurement gas to the variouscontrol and valve actuating chambers in the pump housing component,which are disposed adjacent to the pump chambers and valving chambers ofpumping cartridge 800, when the system is in operation.

In a preferred embodiment, each of the pump modules is configured in asimilar fashion as pump drive system 502 shown previously in FIG. 8,except that pump 516, positive pressure tank 508, and negative pressuretank 512 are not contained in the pump module as suggested in FIG. 8but, instead, in reusable system 1050, pump 516 is replaced by air pump1066, and the pressure tanks are resident in master module 1054 and areshared by the individual pump modules. Each pump module preferablyincludes valves, pressure transducers, and a reference chamber dedicatedto its respective pump chamber. Each pump module also preferablycontains additional pneumatic valves to selectively provide pressurizedmeasurement gas to actuate the various valving chambers associated withits respective pump chamber. In addition, each pump module preferablycontains a dedicated microprocessor for controlling the operation of theindividual pump chamber and performing the various calculationsassociated with the operation of the pump chamber, as discussedpreviously.

Each of the microprocessors included in the various pump modules ispreferably configured to communicate with a microprocessor in mastermodule 1054. Master module 1054 is preferably configured to control thepressure within the positive and negative pressure fluid supply tankspreferably included therein, as well as within the piston bladder andoccluder bladder in door module 1062. The microprocessor included inmaster module 1054 preferably acts as the primary communicationsinterface between the user interface and system control module 1052 andthe individual pump control modules 1056, 1058, and 1060.

Master module 1054 is preferably configured to handle all of theinput/output communications with the user interface/system controlmodule 1052. The commands input master module 1054 from module 1052 canbe processed by the microprocessor of master module 1054 and in turn canbe translated by the microprocessor into appropriate commands for inputto the microprocessors that are resident in individual pump modules1056, 1058, and 1060. In preferred embodiments, overall system controlmodule 1052 includes the majority of application-specific programmingand provides for communication between the reusable system and a user ofthe system. Upon receipt of a command from system control module 1052 bymaster module 1054, the master module is preferably configured to: (1)determine which valves of the system are to be opened or closed; (2)determine which pump module/door module/master module contains thevalves; and (3) issue an appropriate command to open or close suchvalves. All valve mapping (i.e., physical location of the various valvesin the system) that is unique to the operation of the particular pumpingcartridge being utilized, is preferably resident in the microprocessorof master module 1054.

Also, in preferred embodiments, embedded application programming foreach of the microprocessors in the various pump modules may be similar.In some preferred embodiments, there is no application-specificprogramming resident in pump modules 1056, 1058, and 1060. In preferredembodiments, pump modules receive commands from master module 1054 andare configured to determine which commands from master module 1054 toact on and which to ignore based upon whether the specific valves orcomponents which are the subject of the command are resident in theparticular pump module.

It should be appreciated that the overall system architecture describedin FIG. 13 for reusable system 1050 is purely exemplary, and that thoseof ordinary skill in the art will readily envision a wide variety ofother ways to select components and configure and control the system andvarious components thereof, each of which configurations is consideredwithin the scope of the present invention.

Those skilled in the art would readily appreciate that all parametersand configurations described herein are meant to be exemplary and thatactual parameters and configurations will depend upon the specificapplication for which the systems and methods of the present inventionare used. Those skilled in the art will recognize, or be able toascertain using no more than routine experimentation, many equivalentsto the specific embodiments of the invention described herein. It is,therefore, to be understood that the foregoing embodiments are presentedby way of example only and that, within the scope of the appended claimsand equivalents thereto, the invention may be practiced otherwise thanas specifically described. The present invention is directed to eachindividual feature, system, or method described herein. In addition, anycombination of two or more such features, systems, or methods, providedthat such features, systems, or methods are not mutually inconsistent,is included within the scope of the present invention.

What is claimed is:
 1. (canceled)
 2. A medical system for pumping fluidinto or out of a patient via a cartridge, the medical system comprising:the cartridge having a membrane defining a chamber; a pressure source influid communication with the chamber, wherein the pressure source isconfigured to adjust a pressure of the pressure source; a pressuretransducer configured to measure a pressure associated with the pressuresource; a valve configured to isolate the chamber and operativelyconnect the pressure source to the chamber; and a processor within themedical system configured to: adjust the pressure source to apredetermined value; measure a first pressure value of the pressuretransducer; measure a second pressure value of the pressure transducerafter a predetermined amount of time; determine a difference bycomparing the first and second values to each other; and determine anerror condition exists in the medical system if the difference isgreater than a threshold.
 3. The system according to claim 2, whereinthe error condition is a leaky membrane.
 4. The system according toclaim 2, wherein the first pressure value is determined by taking a setof measurements using the pressure transducer.
 5. The system accordingto claim 4, wherein the second pressure value is determined by takinganother set of measurements using the pressure transducer.
 6. The systemaccording to claim 2, wherein the system determines the membrane isunacceptably leaky when the error condition is determined to exist. 7.The system according to claim 2, wherein the pressure source is apressure tank.
 8. The system according to claim 2, wherein the processoris configured to actuate the valve between a first and second positionto thereby isolate the chamber and operatively connect the pressuresource to the chamber.
 9. The system according to claim 8, wherein thefirst pressure value is measured with the valve in the first positionthereby isolating the tank from the chamber.
 10. The system according toclaim 8, wherein the second pressure value is measured with the valve inthe second position thereby fluidly coupling the tank to the chamber.11. The system according to claim 2, wherein the error condition isdetermined to exists if the difference is greater than a predeterminedthreshold.
 12. The system according to claim 2, wherein the errorcondition is a pin-hole in the membrane.
 13. The system according toclaim 2, wherein the error condition is an air leak in the membrane. 14.The system according to claim 2, wherein the predetermined value is apredetermined positive pressure.
 15. The system according to claim 2,wherein the predetermined value is a predetermined negative pressure.16. A medical system for pumping fluid at least one of into and out of apatient using a cartridge, the system comprising: the cartridge having amembrane defining a chamber; a pressure source in fluid communicationwith the chamber, wherein the pressure source is configured to adjust apressure within the pressure source, a pressure transducer configured tomeasure a pressure in operative communication with the pressure source;a valve configured to isolate the chamber and operatively connect thepressure source to the chamber; and a medical system processorconfigured to: adjust the pressure source to a predetermined value;measure a first pressure value of the pressure transducer; measure asecond pressure value of the pressure transducer after a predeterminedamount of time; determine a difference by comparing the first and secondvalues to each other; and leakage-detection means for determiningleakage of the membrane.
 17. The system according to claim 16 whereinthe processor is configured to determine leakage using theleakage-detection means.
 18. A medical system for pumping fluid at leastone of into and out of a patient using a cartridge, the medical systemcomprising: the cartridge having a medical-grade membrane defining achamber; a pressure source in fluid communication with the chamber,wherein the pressure source is configured to adjust a pressureassociated with the pressure source; a pressure transducer configured tomeasure a pressure in operative communication with the pressure source;a valve configured to isolate the chamber and operatively connect thepressure source to the chamber; and a processor in the medical systemconfigured to: adjust the pressure source to a predetermined value;measure a first pressure value of the pressure transducer; measure asecond pressure value of the pressure transducer after a predeterminedamount of time; determine a difference by comparing the first and secondvalues to each other; and pinhole-detection means for detecting apinhole in the membrane.
 19. A medical fluid flow control systemcomprising: a first chamber; a second chamber; a pressure tankcontaining a fluid having a pressure connected to the second chamber; atransducer disposed within the pressure tank for creating a pressuresignal; a valve disposed between the second chamber and the pressuretank; a medical-grade membrane disposed between the first chamber andthe second chamber; a valve controller connected to the valve; a pumpconnected to the pressure tank; and a processor connected to thetransducer, to the pump and to the valve controller for: a) signalingthe valve controller to shut the valve; b) adjusting the pressure of thefluid in the pressure tank with the pump; c) reading the pressure signalfrom the transducer at a first set of predetermined intervals while thevalve is shut creating a first set of pressure signal readings; d)calculating a baseline value based on the first set of pressure signalswhile the valve is shut; e) sending a signal to the valve controller toopen the valve; f) reading the pressure signal from the transducer at asecond set of predetermined timed intervals creating a second set ofpressure signal readings while the valve is open; g) calculating asecond value based on the second set of pressure signals; h) calculatinga leakage rate based on the first and second value; and i) creating analarm signal if the leakage rate exceeds a predefined value.
 20. Thesystem according to claim 19, wherein the alarm signal causes anauditory alarm.
 21. The system according to claim 19, wherein the alarmsignal causes a visual alarm.
 22. The system according to claim 19,wherein the fluid is air.
 23. The system according to claim 19, furthercomprising a memory unit for storing the pressure signals at the firstset of predetermined timed intervals and storing the pressure signals atthe second set of predetermined timed intervals.
 24. The systemaccording to claim 19, wherein the first chamber is disposed within acassette wherein the membrane forms an exterior surface of the cassette.25. A medical system for pumping fluid into or out of a patient via acartridge, the medical system comprising: a cassette holder configuredto receive a cassette a cassette received in the cassette holder, thecassette having a membrane capable of receiving a pressure; a pressuresource configured to be capable of being in fluid communication with thechamber, wherein the pressure source is configured to adjust a pressureof the pressure source; a pressure transducer configured to measure apressure in operative communication with the pressure source; a valveconfigured to isolate the chamber and operatively connect the pressuresource to the chamber; and a processor within the medical systemconfigured to: adjust the pressure source to a predetermined value;measure a first pressure value of the pressure transducer; measure asecond pressure value of the pressure transducer after a predeterminedamount of time; means for leak detection of the membrane.
 26. The systemaccording to claim 25, wherein the means for leak detection of themembrane includes using the processor to determine a difference bycomparing the first and second values to each other.
 27. The systemaccording to claim 26, wherein the means for leak detection of themembrane includes the processor determines a leak exists in the membraneif the difference is greater than a threshold.
 28. A medical system forpumping fluid into or out of a patient via a cartridge, the medicalsystem comprising: a cassette holder configured to receive a cassette acassette received in the cassette holder, the cassette having a membranecapable of receiving a pressure; a pressure source configured to becapable of being in fluid communication with the chamber, wherein thepressure source is configured to adjust a pressure of the pressuresource; a pressure transducer configured to measure a pressure inoperative communication with the pressure source; a valve configured toisolate the chamber and operatively connect the pressure source to thechamber; and a processor within the medical system configured to:actuate the value to first and second positions; adjust the pressuresource to a predetermined value; measure a first pressure value of thepressure transducer; and measure a second pressure value of the pressuretransducer after a predetermined amount of time, wherein the processor,the valve, the pressure source, and the pressure transducer areconfigured to detect a leak of the membrane.
 29. The system according toclaim 28, wherein the processor measures the first pressure value afterthe valve has been in the first position.
 30. The system according toclaim 29, wherein the processor measures the second pressure value afterthe valve has been in the second position.
 31. The system according toclaim 30, wherein the processor measures the second pressure value whilethe valve is in the second position.
 32. The system according to claim29, wherein the processor measures the first pressure value while thevalve is in the first position.